|A skin lesion caused by anthrax|
|Symptoms||Skin form: small blister with surrounding swelling|
Inhalational form: fever, chest pain, shortness of breath
Intestinal form: nausea, vomiting, diarrhea, abdominal pain
Injection form: fever, abscess
|Usual onset||1 day to 2 months post contact|
|Risk factors||Working with animals, travelers, postal workers, military personnel|
|Diagnostic method||Based on antibodies or toxin in the blood, microbial culture|
|Prevention||Anthrax vaccination, antibiotics|
|Prognosis||20–80% die without treatment|
|Frequency||>2,000 cases per year|
Anthrax is an infection caused by the bacterium Bacillus anthracis .It can occur in four forms: skin, lungs, intestinal, and injection. Symptoms begin between one day and two months after the infection is contracted. The skin form presents with a small blister with surrounding swelling that often turns into a painless ulcer with a black center. The inhalation form presents with fever, chest pain, and shortness of breath. The intestinal form presents with diarrhea which may contain blood, abdominal pains, and nausea and vomiting. The injection form presents with fever and an abscess at the site of drug injection.
Bacillus anthracis is the etiologic agent of anthrax—a common disease of livestock and, occasionally, of humans—and the only obligate pathogen within the genus Bacillus. B. anthracis is a Gram-positive, endospore-forming, rod-shaped bacterium, with a width of 1.0–1.2 µm and a length of 3–5 µm. It can be grown in an ordinary nutrient medium under aerobic or anaerobic conditions.
Shortness of breath, also known as dyspnea, is the feeling that one cannot breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity", and recommends evaluating dyspnea by assessing the intensity of the distinct sensations, the degree of distress involved, and its burden or impact on activities of daily living. Distinct sensations include effort/work, chest tightness, and air hunger.
An abscess is a collection of pus that has built up within the tissue of the body. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pressed. The area of redness often extends beyond the swelling. Carbuncles and boils are types of abscess that often involve hair follicles, with carbuncles being larger.
Anthrax is spread by contact with the bacterium's spores, which often appear in infectious animal products.Contact is by breathing, eating, or through an area of broken skin. It does not typically spread directly between people. Risk factors include people who work with animals or animal products, travelers, postal workers, and military personnel. Diagnosis can be confirmed based on finding antibodies or the toxin in the blood or by culture of a sample from the infected site.
An endospore is a dormant, tough, and non-reproductive structure produced by certain bacteria from the phylum Firmicutes. The name "endospore" is suggestive of a spore or seed-like form, but it is not a true spore. It is a stripped-down, dormant form to which the bacterium can reduce itself. Endospore formation is usually triggered by a lack of nutrients, and usually occurs in gram-positive bacteria. In endospore formation, the bacterium divides within its cell wall, and one side then engulfs the other. Endospores enable bacteria to lie dormant for extended periods, even centuries. There are many reports of spores remaining viable over 10,000 years, and revival of spores millions of years old has been claimed. There is one report of viable spores of Bacillus marismortui in salt crystals approximately 250 million years old. When the environment becomes more favorable, the endospore can reactivate itself to the vegetative state. Most types of bacteria cannot change to the endospore form. Examples of bacteria that can form endospores include Bacillus and Clostridium.
Anthrax vaccination is recommended for people who are at high risk of infection.Immunizing animals against anthrax is recommended in areas where previous infections have occurred. Two months of antibiotics such as ciprofloxacin, levofloxacin, and doxycycline after exposure can also prevent infection. If infection occurs treatment is with antibiotics and possibly antitoxin. The type and number of antibiotics used depends on the type of infection. Antitoxin is recommended for those with widespread infection.
Ciprofloxacin is an antibiotic used to treat a number of bacterial infections. This includes bone and joint infections, intra abdominal infections, certain type of infectious diarrhea, respiratory tract infections, skin infections, typhoid fever, and urinary tract infections, among others. For some infections it is used in addition to other antibiotics. It can be taken by mouth, in eye drops, or intravenously.
Levofloxacin, sold under the trade names Levaquin among others, is an antibiotic. It is used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, urinary tract infections, chronic prostatitis, and some types of gastroenteritis. Along with other antibiotics it may be used to treat tuberculosis, meningitis, or pelvic inflammatory disease. Use is generally only recommended when other options are not available. It is available by mouth, intravenously, and in eye drop form.
Doxycycline is an antibiotic that is used in the treatment of infections caused by bacteria and certain other parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, early Lyme disease, cholera, and syphilis. It is also used to prevent malaria and in combination with quinine, to treat malaria. Doxycycline can be used either by mouth or by injection into a vein.
Although a rare disease, human anthrax, when it does occur, is most common in Africa and central and southern Asia.It also occurs more regularly in Southern Europe than elsewhere on the continent, and is uncommon in Northern Europe and North America. Globally, at least 2,000 cases occur a year with about two cases a year in the United States. Skin infections represent more than 95% of cases. Without treatment, the risk of death from skin anthrax is 24%. For intestinal infection, the risk of death is 25 to 75%, while respiratory anthrax has a mortality of 50 to 80%, even with treatment. Until the 20th century, anthrax infections killed hundreds of thousands of people and animals each year. Anthrax has been developed as a weapon by a number of countries. In plant-eating animals, infection occurs when they eat or breathe in the spores while grazing. Carnivores may become infected by eating infected animals.
Southern Europe is the southern region of the European continent. Most definitions of Southern Europe, also known as Mediterranean Europe, include Spain, Italy, Malta, Corsica, Greece, Croatia, Bosnia and Herzegovina, Montenegro, Albania, Kosovo, Slovenia, the East Thrace of European Turkey and Cyprus. Portugal, Andorra, Vatican City, San Marino, Serbia and North Macedonia are also often included despite not having a coast in the Mediterranean. Some definitions may also include mainland Southern France and Monaco, which are otherwise considered parts of Western Europe.
Northern Europe is a general term for the geographical region in Europe that is roughly north of the southern coast of the Baltic Sea, which is about 54°N. Narrower definitions may be based on other geographical factors such as climate and ecology. A broader definition would include the area north of the Alps. Countries which are central-western, central or central-eastern are not usually considered part of either Northern or Southern Europe.
Cutaneous anthrax, also known as hide-porter's disease, is when anthrax occurs on the skin. It is the most common form (>90% of anthrax cases). It is also the least dangerous form (low mortality with treatment, 20% mortality without).Cutaneous anthrax presents as a boil-like skin lesion that eventually forms an ulcer with a black center (eschar). The black eschar often shows up as a large, painless, necrotic ulcer (beginning as an irritating and itchy skin lesion or blister that is dark and usually concentrated as a black dot, somewhat resembling bread mold) at the site of infection. In general, cutaneous infections form within the site of spore penetration between two and five days after exposure. Unlike bruises or most other lesions, cutaneous anthrax infections normally do not cause pain. Nearby lymph nodes may become infected, reddened, swollen, and painful. A scab forms over the lesion soon, and falls off in a few weeks. Complete recovery may take longer. Cutaneous anthrax is typically caused when B. anthracis spores enter through cuts on the skin. This form is found most commonly when humans handle infected animals and/or animal products.
A boil, also called a furuncle, is a deep folliculitis, infection of the hair follicle. It is most commonly caused by infection by the bacterium Staphylococcus aureus, resulting in a painful swollen area on the skin caused by an accumulation of pus and dead tissue. Boils which are expanded are basically pus-filled nodules. Individual boils clustered together are called carbuncles. Most human infections are caused by coagulase-positive S. aureus strains, notable for the bacteria's ability to produce coagulase, an enzyme that can clot blood. Almost any organ system can be infected by S. aureus.
An ulcer is a discontinuity or break in a bodily membrane that impedes the organ of which that membrane is a part from continuing its normal functions. According to Robins pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing out of inflamed necrotic tissue." Common forms of ulcers recognized in medicine include:
An eschar is a slough or piece of dead tissue that is cast off from the surface of the skin, particularly after a burn injury, but also seen in gangrene, ulcer, fungal infections, necrotizing spider bite wounds, spotted fevers and exposure to cutaneous anthrax. The term "eschar" is not interchangeable with "scab". An eschar contains necrotic tissue, whereas a scab is composed of dried blood and exudate.
Cutaneous anthrax is rarely fatal if treated,because the infection area is limited to the skin, preventing the lethal factor, edema factor, and protective antigen from entering and destroying a vital organ. Without treatment, about 20% of cutaneous skin infection cases progress to toxemia and death.
Anthrax lethal factor endopeptidase is an enzyme that catalyzes the hydrolysis of mitogen-activated protein kinase kinases. This enzyme is a component of the lethal factor produced by the bacterium Bacillus anthracis. The preferred cleavage site can be denoted by BBBBxHxH, in which B denotes a basic amino acid Arg or Lys, H denotes a hydrophobic amino acid, and x is any amino acid.
Edema, also spelled oedema or œdema, is an abnormal accumulation of fluid in the interstitium, located beneath the skin and in the cavities of the body, which can cause severe pain. Clinically, edema manifests as swelling. The amount of interstitial fluid is determined by the balance of fluid homeostasis and the increased secretion of fluid into the interstitium. The word is from Greek οἴδημα oídēma meaning "swelling". The condition is also known as dropsy.
In immunology, antigens (Ag) are structures specifically bound by antibodies (Ab) or a cell surface version of Ab ~ B cell antigen receptor (BCR). The terms antigen originally described a structural molecule that binds specifically to an antibody only in the form of native antigen. It was expanded later to refer to any molecule or a linear molecular fragment after processing the native antigen that can be recognized by T-cell receptor (TCR). BCR and TCR are both highly variable antigen receptors diversified by somatic V(D)J recombination. Both T cells and B cells are cellular components of adaptive immunity. The Ag abbreviation stands for an antibody generator.
Respiratory infection in humans is relatively rare and presents as two stages.It infects the lymph nodes in the chest first, rather than the lungs themselves, a condition called hemorrhagic mediastinitis, causing bloody fluid to accumulate in the chest cavity, therefore causing shortness of breath. The first stage causes cold and flu-like symptoms. Symptoms include fever, shortness of breath, cough, fatigue, and chills. This can last hours to days. Often, many fatalities from inhalational anthrax are when the first stage is mistaken for the cold or flu and the victim does not seek treatment until the second stage, which is 90% fatal. The second (pneumonia) stage occurs when the infection spreads from the lymph nodes to the lungs. Symptoms of the second stage develop suddenly after hours or days of the first stage. Symptoms include high fever, extreme shortness of breath, shock, and rapid death within 48 hours in fatal cases. Historical mortality rates were over 85%, but when treated early (seen in the 2001 anthrax attacks), observed case fatality rate dropped to 45%. Distinguishing pulmonary anthrax from more common causes of respiratory illness is essential to avoiding delays in diagnosis and thereby improving outcomes. An algorithm for this purpose has been developed.
Gastrointestinal (GI) infection is most often caused by consuming anthrax-infected meat and is characterized by diarrhea, potentially with blood, abdominal pains, acute inflammation of the intestinal tract, and loss of appetite.Occasional vomiting of blood can occur. Lesions have been found in the intestines and in the mouth and throat. After the bacterium invades the gastrointestinal system, it spreads to the bloodstream and throughout the body, while continuing to make toxins. GI infections can be treated, but usually result in fatality rates of 25% to 60%, depending upon how soon treatment commences. This form of anthrax is the rarest.
Bacillus anthracis is a rod-shaped, Gram-positive, aerobic bacterium about 1 by 9 μm in size. It was shown to cause disease by Robert Koch in 1876 when he took a blood sample from an infected cow, isolated the bacteria, and put them into a mouse. The bacterium normally rests in spore form in the soil, and can survive for decades in this state. Herbivores are often infected whilst grazing, especially when eating rough, irritant, or spiky vegetation; the vegetation has been hypothesized to cause wounds within the GI tract, permitting entry of the bacterial spores into the tissues, though this has not been proven. Once ingested or placed in an open wound, the bacteria begin multiplying inside the animal or human and typically kill the host within a few days or weeks. The spores germinate at the site of entry into the tissues and then spread by the circulation to the lymphatics, where the bacteria multiply.
The production of two powerful exotoxins and lethal toxin by the bacteria causes death. Veterinarians can often tell a possible anthrax-induced death by its sudden occurrence, and by the dark, nonclotting blood that oozes from the body orifices. Most anthrax bacteria inside the body after death are outcompeted and destroyed by anaerobic bacteria within minutes to hours post mortem. However, anthrax vegetative bacteria that escape the body via oozing blood or through the opening of the carcass may form hardy spores. These vegetative bacteria are not contagious.One spore forms per one vegetative bacterium. The triggers for spore formation are not yet known, though oxygen tension and lack of nutrients may play roles. Once formed, these spores are very hard to eradicate.
The infection of herbivores (and occasionally humans) by the inhalational route normally proceeds as: Once the spores are inhaled, they are transported through the air passages into the tiny air sacs (alveoli) in the lungs. The spores are then picked up by scavenger cells (macrophages) in the lungs and are transported through small vessels (lymphatics) to the lymph nodes in the central chest cavity (mediastinum). Damage caused by the anthrax spores and bacilli to the central chest cavity can cause chest pain and difficulty in breathing. Once in the lymph nodes, the spores germinate into active bacilli that multiply and eventually burst the macrophages, releasing many more bacilli into the bloodstream to be transferred to the entire body. Once in the blood stream, these bacilli release three proteins named lethal factor, edema factor, and protective antigen. The three are not toxic by themselves, but their combination is incredibly lethal to humans.Protective antigen combines with these other two factors to form lethal toxin and edema toxin, respectively. These toxins are the primary agents of tissue destruction, bleeding, and death of the host. If antibiotics are administered too late, even if the antibiotics eradicate the bacteria, some hosts still die of toxemia because the toxins produced by the bacilli remain in their systems at lethal dose levels.
The spores of anthrax are able to survive in harsh conditions for decades or even centuries.Such spores can be found on all continents, including Antarctica. Disturbed grave sites of infected animals have been known to cause infection after 70 years.
Occupational exposure to infected animals or their products (such as skin, wool, and meat) is the usual pathway of exposure for humans. Workers who are exposed to dead animals and animal products are at the highest risk, especially in countries where anthrax is more common. Anthrax in livestock grazing on open range where they mix with wild animals still occasionally occurs in the United States and elsewhere. Many workers who deal with wool and animal hides are routinely exposed to low levels of anthrax spores, but most exposure levels are not sufficient to develop anthrax infections. A lethal infection is reported to result from inhalation of about 10,000–20,000 spores, though this dose varies among host species.Little documented evidence is available to verify the exact or average number of spores needed for infection.
Historically, inhalational anthrax was called woolsorters' disease because it was an occupational hazard for people who sorted wool. Today, this form of infection is extremely rare in advanced nations, as almost no infected animals remain.
Anthrax can enter the human body through the intestines (ingestion), lungs (inhalation), or skin (cutaneous) and causes distinct clinical symptoms based on its site of entry. In general, an infected human is quarantined. However, anthrax does not usually spread from an infected human to an uninfected human.If the disease is fatal to the person's body, though, its mass of anthrax bacilli becomes a potential source of infection to others and special precautions should be used to prevent further contamination. Inhalational anthrax, if left untreated until obvious symptoms occur, is usually fatal.
Anthrax can be contracted in laboratory accidents or by handling infected animals, their wool, or their hides.It has also been used in biological warfare agents and by terrorists to intentionally infect as exemplified by the 2001 anthrax attacks.
The lethality of the anthrax disease is due to the bacterium's two principal virulence factors: the poly-D-glutamic acid capsule, which protects the bacterium from phagocytosis by host neutrophils, and the tripartite protein toxin, called anthrax toxin. Anthrax toxin is a mixture of three protein components: protective antigen (PA), edema factor (EF), and lethal factor (LF).PA plus LF produces lethal toxin, and PA plus EF produces edema toxin. These toxins cause death and tissue swelling (edema), respectively.
To enter the cells, the edema and lethal factors use another protein produced by B. anthracis called protective antigen, which binds to two surface receptors on the host cell. A cell protease then cleaves PA into two fragments: PA20 and PA63. PA20 dissociates into the extracellular medium, playing no further role in the toxic cycle. PA63 then oligomerizes with six other PA63 fragments forming a heptameric ring-shaped structure named a prepore. Once in this shape, the complex can competitively bind up to three EFs or LFs, forming a resistant complex.Receptor-mediated endocytosis occurs next, providing the newly formed toxic complex access to the interior of the host cell. The acidified environment within the endosome triggers the heptamer to release the LF and/or EF into the cytosol. It is unknown how exactly the complex results in the death of the cell.
Edema factor is a calmodulin-dependent adenylate cyclase. Adenylate cyclase catalyzes the conversion of ATP into cyclic AMP (cAMP) and pyrophosphate. The complexation of adenylate cyclase with calmodulin removes calmodulin from stimulating calcium-triggered signaling, thus inhibiting the immune response.To be specific, LF inactivates neutrophils (a type of phagocytic cell) by the process just described so they cannot phagocytose bacteria. Throughout history, lethal factor was presumed to cause macrophages to make TNF-alpha and interleukin 1, beta (IL1B). TNF-alpha is a cytokine whose primary role is to regulate immune cells, as well as to induce inflammation and apoptosis or programmed cell death. Interleukin 1, beta is another cytokine that also regulates inflammation and apoptosis. The overproduction of TNF-alpha and IL1B ultimately leads to septic shock and death. However, recent evidence indicates anthrax also targets endothelial cells that line serous cavities such as the pericardial cavity, pleural cavity, and peritoneal cavity, lymph vessels, and blood vessels, causing vascular leakage of fluid and cells, and ultimately hypovolemic shock and septic shock.
Various techniques may be used for the direct identification of B. anthracis in clinical material. Firstly, specimens may be Gram stained. Bacillus spp. are quite large in size (3 to 4 μm long), they may grow in long chains, and they stain Gram-positive. To confirm the organism is B. anthracis, rapid diagnostic techniques such as polymerase chain reaction-based assays and immunofluorescence microscopy may be used.
All Bacillus species grow well on 5% sheep blood agar and other routine culture media. Polymyxin-lysozyme-EDTA-thallous acetate can be used to isolate B. anthracis from contaminated specimens, and bicarbonate agar is used as an identification method to induce capsule formation. Bacillus spp. usually grow within 24 hours of incubation at 35 °C, in ambient air (room temperature) or in 5% CO2. If bicarbonate agar is used for identification, then the medium must be incubated in 5% CO2. B. anthracis colonies are medium-large, gray, flat, and irregular with swirling projections, often referred to as having a "medusa head" appearance, and are not hemolytic on 5% sheep blood agar. The bacteria are not motile, susceptible to penicillin, and produce a wide zone of lecithinase on egg yolk agar. Confirmatory testing to identify B. anthracis includes gamma bacteriophage testing, indirect hemagglutination, and enzyme-linked immunosorbent assay to detect antibodies. The best confirmatory precipitation test for anthrax is the Ascoli test.
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If a person is suspected as having died from anthrax, precautions should be taken to avoid skin contact with the potentially contaminated body and fluids exuded through natural body openings. The body should be put in strict quarantine. A blood sample should then be collected and sealed in a container and analyzed in an approved laboratory to ascertain if anthrax is the cause of death. Then, the body should be incinerated. Microscopic visualization of the encapsulated bacilli, usually in very large numbers, in a blood smear stained with polychrome methylene blue (McFadyean stain) is fully diagnostic, though culture of the organism is still the gold standard for diagnosis. Full isolation of the body is important to prevent possible contamination of others. Protective, impermeable clothing and equipment such as rubber gloves, rubber apron, and rubber boots with no perforations should be used when handling the body. No skin, especially if it has any wounds or scratches, should be exposed. Disposable personal protective equipment is preferable, but if not available, decontamination can be achieved by autoclaving. Disposable personal protective equipment and filters should be autoclaved, and/or burned and buried. Anyone working with anthrax in a suspected or confirmed person should wear respiratory equipment capable of filtering particles of their size or smaller. The US National Institute for Occupational Safety and Health – and Mine Safety and Health Administration-approved high-efficiency respirator, such as a half-face disposable respirator with a high-efficiency particulate air filter, is recommended.All possibly contaminated bedding or clothing should be isolated in double plastic bags and treated as possible biohazard waste. The body of an infected person should be sealed in an airtight body bag. Dead people who are opened and not burned provide an ideal source of anthrax spores. Cremating people is the preferred way of handling body disposal. No embalming or autopsy should be attempted without a fully equipped biohazard laboratory and trained, knowledgeable personnel.
Vaccines against anthrax for use in livestock and humans have had a prominent place in the history of medicine. The French scientist Louis Pasteur developed the first effective vaccine in 1881.Human anthrax vaccines were developed by the Soviet Union in the late 1930s and in the US and UK in the 1950s. The current FDA-approved US vaccine was formulated in the 1960s.
Currently administered human anthrax vaccines include acellular (United States) and live vaccine (Russia) varieties. All currently used anthrax vaccines show considerable local and general reactogenicity (erythema, induration, soreness, fever) and serious adverse reactions occur in about 1% of recipients.The American product, BioThrax, is licensed by the FDA and was formerly administered in a six-dose primary series at 0, 2, 4 weeks and 6, 12, 18 months, with annual boosters to maintain immunity. In 2008, the FDA approved omitting the week-2 dose, resulting in the currently recommended five-dose series. New second-generation vaccines currently being researched include recombinant live vaccines and recombinant subunit vaccines. In the 20th century the use of a modern product (BioThrax) to protect American troops against the use of anthrax in biological warfare was controversial.
Preventive antibiotics are recommended in those who have been exposed.Early detection of sources of anthrax infection can allow preventive measures to be taken. In response to the anthrax attacks of October 2001, the United States Postal Service (USPS) installed biodetection systems (BDSs) in their large-scale mail processing facilities. BDS response plans were formulated by the USPS in conjunction with local responders including fire, police, hospitals, and public health. Employees of these facilities have been educated about anthrax, response actions, and prophylactic medication. Because of the time delay inherent in getting final verification that anthrax has been used, prophylactic antibiotic treatment of possibly exposed personnel must be started as soon as possible.
This section contains instructions, advice, or how-to content . (February 2018)
Anthrax cannot be spread directly from person to person, but a person's clothing and body may be contaminated with anthrax spores. Effective decontamination of people can be accomplished by a thorough wash-down with antimicrobial soap and water. Waste water should be treated with bleach or another antimicrobial agent.Effective decontamination of articles can be accomplished by boiling them in water for 30 minutes or longer. Chlorine bleach is ineffective in destroying spores and vegetative cells on surfaces, though formaldehyde is effective. Burning clothing is very effective in destroying spores. After decontamination, there is no need to immunize, treat, or isolate contacts of persons ill with anthrax unless they were also exposed to the same source of infection.
Early antibiotic treatment of anthrax is essential; delay significantly lessens chances for survival.
Treatment for anthrax infection and other bacterial infections includes large doses of intravenous and oral antibiotics, such as fluoroquinolones (ciprofloxacin), doxycycline, erythromycin, vancomycin, or penicillin. FDA-approved agents include ciprofloxacin, doxycycline, and penicillin.
In possible cases of pulmonary anthrax, early antibiotic prophylaxis treatment is crucial to prevent possible death.
In recent years, many attempts have been made to develop new drugs against anthrax, but existing drugs are effective if treatment is started soon enough.
In May 2009, Human Genome Sciences submitted a biologic license application (BLA, permission to market) for its new drug, raxibacumab (brand name ABthrax) intended for emergency treatment of inhaled anthrax.On 14 December 2012, the US Food and Drug Administration approved raxibacumab injection to treat inhalational anthrax. Raxibacumab is a monoclonal antibody that neutralizes toxins produced by B. anthracis. On March, 2016, FDA approved a second anthrax treatment using a monoclonal antibody which neutralizes the toxins produced by B. anthracis. Obiltoxaximab is approved to treat inhalational anthrax in conjunction with appropriate antibacterial drugs, and for prevention when alternative therapies are not available or appropriate.
Globally, at least 2,000 cases occur a year.
The last fatal case of natural inhalational anthrax in the United States occurred in California in 1976, when a home weaver died after working with infected wool imported from Pakistan. To minimize the chance of spreading the disease, the deceased was transported to UCLA in a sealed plastic body bag within a sealed metal container for autopsy.
Gastrointestinal anthrax is exceedingly rare in the United States, with two cases on record, the first was reported in 1942, according to the Centers for Disease Control and Prevention.
During December 2009, the New Hampshire Department of Health and Human Services confirmed a case of gastrointestinal anthrax in an adult female. The CDC investigated the source and the possibility that it was contracted from an African drum recently used by the woman taking part in a drum circle.The woman apparently inhaled anthrax [in spore form] from the hide of the drum. She became critically ill, but with gastrointestinal anthrax rather than inhaled anthrax, which made her unique in American medical history. The building where the infection took place was cleaned and reopened to the public and the woman recovered. Jodie Dionne-Odom, New Hampshire state epidemiologist, stated, "It is a mystery. We really don't know why it happened."
In November 2008, a drum maker in the United Kingdom who worked with untreated animal skins died from anthrax.In December 2009, an outbreak of anthrax occurred amongst heroin addicts in the Glasgow and Stirling areas of Scotland, resulting in 14 deaths. The source of the anthrax is believed to be dilution of the heroin with bone meal in Afghanistan.
The English name comes from anthrax (ἄνθραξ), the Greek word for coal, possibly having Egyptian etymology, because of the characteristic black skin lesions developed by victims with a cutaneous anthrax infection. The central, black eschar, surrounded by vivid red skin has long been recognised as typical of the disease. The first recorded use of the word "anthrax" in English is in a 1398 translation of Bartholomaeus Anglicus' work De proprietatibus rerum (On the Properties of Things, 1240).
Anthrax has been known by a wide variety of names, indicating its symptoms, location and groups considered most vulnerable to infection. These include Siberian plague, Cumberland disease, charbon, splenic fever, malignant edema, woolsorter's disease, and even la maladie de Bradford .
Robert Koch, a German physician and scientist, first identified the bacterium that caused the anthrax disease in 1875 in Wolsztyn (now part of Poland).His pioneering work in the late 19th century was one of the first demonstrations that diseases could be caused by microbes. In a groundbreaking series of experiments, he uncovered the lifecycle and means of transmission of anthrax. His experiments not only helped create an understanding of anthrax, but also helped elucidate the role of microbes in causing illness at a time when debates still took place over spontaneous generation versus cell theory. Koch went on to study the mechanisms of other diseases and won the 1905 Nobel Prize in Physiology or Medicine for his discovery of the bacterium causing tuberculosis.
Although Koch arguably made the greatest theoretical contribution to understanding anthrax, other researchers were more concerned with the practical questions of how to prevent the disease. In Britain, where anthrax affected workers in the wool, worsted, hides, and tanning industries, it was viewed with fear. John Henry Bell, a doctor based in Bradford, first made the link between the mysterious and deadly "woolsorter's disease" and anthrax, showing in 1878 that they were one and the same.In the early 20th century, Friederich Wilhelm Eurich, the German bacteriologist who settled in Bradford with his family as a child, carried out important research for the local Anthrax Investigation Board. Eurich also made valuable contributions to a Home Office Departmental Committee of Inquiry, established in 1913 to address the continuing problem of industrial anthrax. His work in this capacity, much of it collaboration with the factory inspector G. Elmhirst Duckering, led directly to the Anthrax Prevention Act (1919).
Anthrax posed a major economic challenge in France and elsewhere during the 19th century. Horses, cattle, and sheep were particularly vulnerable, and national funds were set aside to investigate the production of a vaccine. Noted French scientist Louis Pasteur was charged with the production of a vaccine, following his successful work in developing methods which helped to protect the important wine and silk industries.
In May 1881, Pasteur – in collaboration with his assistants Jean-Joseph Henri Toussaint, Émile Roux and others – performed a public experiment at Pouilly-le-Fort to demonstrate his concept of vaccination. He prepared two groups of 25 sheep, one goat, and several cattle. The animals of one group were injected with an anthrax vaccine prepared by Pasteur twice, at an interval of 15 days; the control group was left unvaccinated. Thirty days after the first injection, both groups were injected with a culture of live anthrax bacteria. All the animals in the unvaccinated group died, while all of the animals in the vaccinated group survived.
After this apparent triumph, which was widely reported in the local, national, and international press, Pasteur made strenuous efforts to export the vaccine beyond France. He used his celebrity status to establish Pasteur Institutes across Europe and Asia, and his nephew, Adrien Loir, travelled to Australia in 1888 to try to introduce the vaccine to combat anthrax in New South Wales.Ultimately, the vaccine was unsuccessful in the challenging climate of rural Australia, and it was soon superseded by a more robust version developed by local researchers John Gunn and John McGarvie Smith.
The human vaccine for anthrax became available in 1954. This was a cell-free vaccine instead of the live-cell Pasteur-style vaccine used for veterinary purposes. An improved cell-free vaccine became available in 1970.
Anthrax spores can survive for very long periods of time in the environment after release. Chemical methods for cleaning anthrax-contaminated sites or materials may use oxidizing agents such as peroxides, ethylene oxide, Sandia Foam,chlorine dioxide (used in the Hart Senate Office Building) , peracetic acid, ozone gas, hypochlorous acid, sodium persulfate, and liquid bleach products containing sodium hypochlorite. Nonoxidizing agents shown to be effective for anthrax decontamination include methyl bromide, formaldehyde, and metam sodium. These agents destroy bacterial spores. All of the aforementioned anthrax decontamination technologies have been demonstrated to be effective in laboratory tests conducted by the US EPA or others. A bleach solution for treating hard surfaces has been approved by the EPA.
Chlorine dioxide has emerged as the preferred biocide against anthrax-contaminated sites, having been employed in the treatment of numerous government buildings over the past decade.Its chief drawback is the need for in situ processes to have the reactant on demand.
To speed the process, trace amounts of a nontoxic catalyst composed of iron and tetroamido macrocyclic ligands are combined with sodium carbonate and bicarbonate and converted into a spray. The spray formula is applied to an infested area and is followed by another spray containing tert-butyl hydroperoxide.
Using the catalyst method, a complete destruction of all anthrax spores can be achieved in under 30 minutes.A standard catalyst-free spray destroys fewer than half the spores in the same amount of time.
Cleanups at a Senate Office Building, several contaminated postal facilities, and other US government and private office buildings, a collaborative effort headed by the Environmental Protection Agency million, according to the Government Accountability Office. Cleaning the Brentwood postal facility in Washington cost $130 million and took 26 months. Since then, newer and less costly methods have been developed.showed decontamination to be possible, but time-consuming and costly. Clearing the Senate Office Building of anthrax spores cost $27
Cleanup of anthrax-contaminated areas on ranches and in the wild is much more problematic. Carcasses may be burned,though often 3 days are needed to burn a large carcass and this is not feasible in areas with little wood. Carcasses may also be buried, though the burying of large animals deeply enough to prevent resurfacing of spores requires much manpower and expensive tools. Carcasses have been soaked in formaldehyde to kill spores, though this has environmental contamination issues. Block burning of vegetation in large areas enclosing an anthrax outbreak has been tried; this, while environmentally destructive, causes healthy animals to move away from an area with carcasses in search of fresh grass. Some wildlife workers have experimented with covering fresh anthrax carcasses with shadecloth and heavy objects. This prevents some scavengers from opening the carcasses, thus allowing the putrefactive bacteria within the carcass to kill the vegetative B. anthracis cells and preventing sporulation. This method also has drawbacks, as scavengers such as hyenas are capable of infiltrating almost any exclosure.
The experimental site at Gruinard Island is said to have been decontaminated with a mixture of formaldehyde and seawater by the Ministry of Defence.It is not clear whether similar treatments had been applied to US test sites.
Anthrax spores have been used as a biological warfare weapon. Its first modern incidence occurred when Nordic rebels, supplied by the German General Staff, used anthrax with unknown results against the Imperial Russian Army in Finland in 1916.Anthrax was first tested as a biological warfare agent by Unit 731 of the Japanese Kwantung Army in Manchuria during the 1930s; some of this testing involved intentional infection of prisoners of war, thousands of whom died. Anthrax, designated at the time as Agent N, was also investigated by the Allies in the 1940s.
A long history of practical bioweapons research exists in this area. For example, in 1942, British bioweapons trials severely contaminated Gruinard Island in Scotland with anthrax spores of the Vollum-14578 strain, making it a no-go area until it was decontaminated in 1990. – a biological weapon containing dried anthrax spores. Additionally, five million "cattle cakes" (animal feed pellets impregnated with anthrax spores) were prepared and stored at Porton Down for "Operation Vegetarian" – antilivestock attacks against Germany to be made by the Royal Air Force. The plan was for anthrax-based biological weapons to be dropped on Germany in 1944. However, the edible cattle cakes and the bomb were not used; the cattle cakes were incinerated in late 1945.The Gruinard trials involved testing the effectiveness of a submunition of an "N-bomb"
Weaponized anthrax was part of the US stockpile prior to 1972, when the United States signed the Biological Weapons Convention.President Nixon ordered the dismantling of US biowarfare programs in 1969 and the destruction of all existing stockpiles of bioweapons. In 1978–79, the Rhodesian government used anthrax against cattle and humans during its campaign against rebels. The Soviet Union created and stored 100 to 200 tons of anthrax spores at Kantubek on Vozrozhdeniya Island. They were abandoned in 1992 and destroyed in 2002.
American military and British Army personnel are routinely vaccinated against anthrax prior to active service in places where biological attacks are considered a threat.
Despite signing the 1972 agreement to end bioweapon production, the government of the Soviet Union had an active bioweapons program that included the production of hundreds of tons of weapons-grade anthrax after this period. On 2 April 1979, some of the over one million people living in Sverdlovsk (now called Ekaterinburg, Russia), about 850 miles (1,370 km) east of Moscow, were exposed to an accidental release of anthrax from a biological weapons complex located near there. At least 94 people were infected, of whom at least 68 died. One victim died four days after the release, 10 over an eight-day period at the peak of the deaths, and the last six weeks later. Extensive cleanup, vaccinations, and medical interventions managed to save about 30 of the victims. Extensive cover-ups and destruction of records by the KGB continued from 1979 until Russian President Boris Yeltsin admitted this anthrax accident in 1992. Jeanne Guillemin reported in 1999 that a combined Russian and United States team investigated the accident in 1992.
Nearly all of the night-shift workers of a ceramics plant directly across the street from the biological facility (compound 19) became infected, and most died. Since most were men, some NATO governments suspected the Soviet Union had developed a sex-specific weapon.The government blamed the outbreak on the consumption of anthrax-tainted meat, and ordered the confiscation of all uninspected meat that entered the city. They also ordered all stray dogs to be shot and people not have contact with sick animals. Also, a voluntary evacuation and anthrax vaccination program was established for people from 18–55.
To support the cover-up story, Soviet medical and legal journals published articles about an outbreak in livestock that caused GI anthrax in people having consumed infected meat, and cutaneous anthrax in people having come into contact with the animals. All medical and public health records were confiscated by the KGB.In addition to the medical problems the outbreak caused, it also prompted Western countries to be more suspicious of a covert Soviet bioweapons program and to increase their surveillance of suspected sites. In 1986, the US government was allowed to investigate the incident, and concluded the exposure was from aerosol anthrax from a military weapons facility. In 1992, President Yeltsin admitted he was "absolutely certain" that "rumors" about the Soviet Union violating the 1972 Bioweapons Treaty were true. The Soviet Union, like the US and UK, had agreed to submit information to the UN about their bioweapons programs, but omitted known facilities and never acknowledged their weapons program.
In theory, anthrax spores can be cultivated with minimal special equipment and a first-year collegiate microbiological education.To make large amounts of an aerosol form of anthrax suitable for biological warfare requires extensive practical knowledge, training, and highly advanced equipment.
Concentrated anthrax spores were used for bioterrorism in the 2001 anthrax attacks in the United States, delivered by mailing postal letters containing the spores.The letters were sent to several news media offices and two Democratic senators: Tom Daschle of South Dakota and Patrick Leahy of Vermont. As a result, 22 were infected and five died. Only a few grams of material were used in these attacks and in August 2008, the US Department of Justice announced they believed that Bruce Ivins, a senior biodefense researcher employed by the United States government, was responsible. These events also spawned many anthrax hoaxes.
Due to these events, the US Postal Service installed biohazard detection systems at its major distribution centers to actively scan for anthrax being transported through the mail.As of 2013, positive alerts by these systems have occurred.
In response to the postal anthrax attacks and hoaxes, the United States Postal Service sterilized some mail using gamma irradiation and treatment with a proprietary enzyme formula supplied by Sipco Industries.
A scientific experiment performed by a high school student, later published in the Journal of Medical Toxicology, suggested a domestic electric iron at its hottest setting (at least 400 °F (204 °C)) used for at least 5 minutes should destroy all anthrax spores in a common postal envelope.
Anthrax attacks have featured in the storylines of various television episodes and films. A Criminal Minds episode follows the attempt to identify an attacker who released anthrax spores in a public park.
Anthrax is especially rare in dogs and cats, as is evidenced by a single reported case in the United States in 2001.Anthrax outbreaks occur in some wild animal populations with some regularity.
Russian researchers estimate arctic permafrost contains around 1.5 million anthrax-infected reindeer carcasses, and the spores may survive in the permafrost for 105 years. A risk exists that global warming in the Arctic can thaw the permafrost, releasing anthrax spores in the carcasses. In 2016, an anthrax outbreak in reindeer was linked to a 75-year-old carcass that defrosted during a heat wave.
Bioterrorism is terrorism involving the intentional release or dissemination of biological agents. These agents are bacteria, viruses, fungi, or toxins, and may be in a naturally occurring or a human-modified form, in much the same way in biological warfare.
Botulism is a rare and potentially fatal illness caused by a toxin produced by the bacterium Clostridium botulinum. The disease begins with weakness, blurred vision, feeling tired, and trouble speaking. This may then be followed by weakness of the arms, chest muscles, and legs. Vomiting, swelling of the abdomen, and diarrhea may also occur. The disease does not usually affect consciousness or cause a fever.
Diphtheria is an infection caused by the bacterium Corynebacterium diphtheriae. Signs and symptoms may vary from mild to severe. They usually start two to five days after exposure. Symptoms often come on fairly gradually, beginning with a sore throat and fever. In severe cases, a grey or white patch develops in the throat. This can block the airway and create a barking cough as in croup. The neck may swell in part due to enlarged lymph nodes. A form of diphtheria that involves the skin, eyes, or genitals also exists. Complications may include myocarditis, inflammation of nerves, kidney problems, and bleeding problems due to low levels of platelets. Myocarditis may result in an abnormal heart rate and inflammation of the nerves may result in paralysis.
Biological hazards, also known as biohazards, refer to biological substances that pose a threat to the health of living organisms, primarily that of humans. This can include samples of a microorganism, virus or toxin that can affect human health. It can also include substances harmful to other animals.
Scarlet fever is a disease which can occur as a result of a group A Streptococcus infection. The signs and symptoms include a sore throat, fever, headaches, swollen lymph nodes, and a characteristic rash. The rash is red and feels like sandpaper and the tongue may be red and bumpy. It most commonly affects children between five and 15 years of age.
Tularemia, also known as rabbit fever, is an infectious disease caused by the bacterium Francisella tularensis. Symptoms may include fever, skin ulcers, and enlarged lymph nodes. Occasionally, a form that results in pneumonia or a throat infection may occur.
Francisella tularensis is a pathogenic species of Gram-negative coccobacillus, an aerobic bacterium. It is non-spore forming, non-motile and the causative agent of tularemia, the pneumonic form of which is often lethal without treatment. It is a fastidious, facultative intracellular bacterium which requires cysteine for growth. Due to its low infectious dose, ease of spread by aerosol, and high virulence, F. tularensis is classified as a Tier 1 Select Agent by the U.S. government, along with other potential agents of bioterrorism such as Yersinia pestis, Bacillus anthracis and Ebola virus. When found in nature, Francisella tularensis can survive for several weeks at low temperatures in animal carcasses, soil, and water. In laboratory, F. tularensis appears as small rods, and is grown best at 35-37°C.
Dermatophytosis, also known as ringworm, is a fungal infection of the skin. Typically it results in a red, itchy, scaly, circular rash. Hair loss may occur in the area affected. Symptoms begin four to fourteen days after exposure. Multiple areas can be affected at a given time.
Vaccines against the livestock and human disease anthrax—caused by the bacterium Bacillus anthracis—have had a prominent place in the history of medicine, from Pasteur’s pioneering 19th-century work with cattle to the controversial late 20th century use of a modern product to protect American troops against the use of anthrax in biological warfare. Human anthrax vaccines were developed by the Soviet Union in the late 1930s and in the US and UK in the 1950s. The current vaccine approved by the U.S. Food and Drug Administration (FDA) was formulated in the 1960s.
Blackleg, black quarter, quarter evil, or quarter ill is an infectious bacterial disease most commonly caused by Clostridium chauvoei, a Gram-positive bacterial species. It is seen in livestock all over the world, usually affecting cattle, sheep, and goats. It has been seen occasionally in farmed bison and deer. The acute nature of the disease makes successful treatment difficult, and the efficacy of the commonly used vaccine is disputed.
Artificial induction of immunity is the artificial induction of immunity to specific diseases – making people immune to disease by means other than waiting for them to catch the disease. The purpose is to reduce the risk of death and suffering.
Anthrax toxin is a three-protein exotoxin secreted by virulent strains of the bacterium, Bacillus anthracis—the causative agent of anthrax. The toxin was first discovered by Harry Smith in 1954. Anthrax toxin is composed of a cell-binding protein, known as protective antigen (PA), and two enzyme components, called edema factor (EF) and lethal factor (LF). These three protein components act together to impart their physiological effects. Assembled complexes containing the toxin components are endocytosed. In the endosome, the enzymatic components of the toxin translocate into the cytoplasm of a target cell. Once in the cytosol, the enzymatic components of the toxin disrupts various immune cell functions, namely cellular signaling and cell migration. The toxin may even induce cell lysis, as is observed for macrophage cells. Anthrax toxin allows the bacteria to evade the immune system, proliferate, and ultimately kill the host animal. Research on anthrax toxin also provides insight into the generation of macromolecular assemblies, and on protein translocation, pore formation, endocytosis, and other biochemical processes.
Raxibacumab is a human monoclonal antibody intended for the prophylaxis and treatment of inhaled anthrax. Its efficacy has been proven in rabbits and monkeys. In December 2012 raxibacumab was approved for the treatment of inhalational anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs, and for prophylaxis of inhalational anthrax when alternative therapies are not available or are not appropriate.Approval Letter
Building 470 — also called the Pilot Plant, or sometimes “the Tower”, or “Anthrax Tower” — was a seven-story steel and brick building at Fort Detrick in Frederick, Maryland, USA, used in the small-scale production of biological warfare (BW) agents. The building, a Cold War era structure, was transferred from the Department of Defense to the National Cancer Institute-Frederick in 1988, to which it belonged until 2003 when it was demolished.
Clostridium tetani is a common soil bacterium and the causative agent of tetanus. When growing in soil, C. tetani are rod-shaped and up to 2.5 micrometres long. However, when forming spores C. tetani becomes substantially enlarged at one end, resembling tennis rackets or drumsticks. C. tetani spores are extremely hardy and can be found globally in soil or in the gastrointestinal tract of animals. If inoculated into a wound, C. tetani can grow and produce a potent toxin, tetanospasmin, which interferes with motor neurons, causing tetanus. All mammals are susceptible to the disease. The toxin's action can be prevented with tetanus toxoid vaccines, which are often administered to children worldwide.
The spoilage of meat occurs, if the meat is untreated, in a matter of hours or days and results in the meat becoming unappetizing, poisonous, or infectious. Spoilage is caused by the practically unavoidable infection and subsequent decomposition of meat by bacteria and fungi, which are borne by the animal itself, by the people handling the meat, and by their implements. Meat can be kept edible for a much longer time – though not indefinitely – if proper hygiene is observed during production and processing, and if appropriate food safety, food preservation and food storage procedures are applied.
Clostridium histolyticum is a species of bacteria found in feces and the soil. It is a motile, gram-positive, aerotolerant anaerobe. C. histolyticum is pathogenic in many species, including guinea pigs, mice, and rabbits, and humans. C. histolyticum has been shown to cause gas gangrene, often in association with other bacteria species.
Anthrax vaccine adsorbed (AVA) is the only FDA-licensed human anthrax vaccine in the United States. It is produced under the trade name BioThrax by the Emergent BioDefense Corporation in Lansing, Michigan. The parent company of Emergent BioDefense is Emergent BioSolutions of Rockville, Maryland. It is sometimes called MDPH-PA or MDPH-AVA after the former Michigan Department of Public Health, which formerly was involved in its production.
For the attacks of 2001, CFR was only 45%, while before this time CFRs for IA were >85% (Page 37)
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