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. mechanism 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 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. diagnosis possible edema and necrosis in a case of injection anthrax. 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. prevention precautions are taken to avoid contact with the skin and any fluids exuded through natural body openings of a deceased body that is suspected of harboring anthrax. the body should be put in strict quarantine. a blood sample is collected and sealed in a container and analyzed in an approved laboratory to ascertain if anthrax is the cause of death. the body should be sealed in an airtight body bag and incinerated to prevent the transmission of anthrax spores. 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 the 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 are 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. used disposable equipment is burned and/or buried after use. all contaminated bedding or clothing is isolated in double plastic bags and treated as biohazard waste. respiratory equipment capable of filtering small particles, such the us national institute for occupational safety and health- and mine safety and health administration-approved high-efficiency respirator, is worn. vaccines main article: anthrax vaccines 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. this five-dose series is available to military personnel, scientists who work with anthrax and members of the public who do jobs which cause them to be at-risk. 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. antibiotics 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. treatment anthrax cannot be spread from person to person, except in the rare case of skin exudates from cutaneous anthrax. however, 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. wastewater is 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. antibiotics 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. many attempts have been made to develop new drugs against anthrax, but existing drugs are effective if treatment is started soon enough. monoclonal antibodies 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. in 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. prognosis 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, up to 20% of cutaneous skin infection cases progress to toxemia and death. before 2001, fatality rates for inhalation anthrax were 90%; since then, they have fallen to 45%. people that progress to the fulminant phase of inhalational anthrax nearly always die, with one case study showing a death rate of 97%. anthrax meningoencephalitis is also nearly always fatal. gastrointestinal anthrax infections can be treated, but usually result in fatality rates of 25% to 60%, depending upon how soon treatment commences. injection anthrax is the rarest form of anthrax, and has only been seen to have occurred in a group of heroin injecting drug users. epidemiology globally, at least 2,000 cases occur a year. united states 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 body 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 only two cases on record. the first case 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. in 2007 two cases of cutaneous anthrax were reported in danbury, connecticut. the case involved a maker of traditional african-style drums who was working with a goat hide purchased from a dealer in new york city which had been previously cleared by customs. while the hide was being scraped, a spider bite led to the spores entering the bloodstream. his son also became infected. the cdc investigated the source of the december 2009 infection 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. the new hampshire state epidemiologist, jodie dionne-odom, stated "it is a mystery. we really don't know why it happened." croatia in july 2022, dozens of cattle in a nature park in lonjsko polje, a flood plain by the sava river, died of anthrax and 6 people have been hospitalized with light, skin-related symptoms. united kingdom in november 2008, a drum