Anthrax

Anthrax, also referred to as splenic fever, is an acute infectious disease caused by the bacteria Bacillus anthracis and is highly lethal in some forms. Anthrax most commonly occurs in wild and domestic herbivores, but it can also occur in humans when they are exposed to infected animals, tissue from infected animals, or high concentrations of anthrax spores. There are no known cases of infection in humans resulting from direct contact with a diseased person. The word anthrax is derived from the Greek word anthrakis, or "coal", in reference to the black skin lesions victims develop.

Overview
Anthrax infection is rare in humans though occasionally occurs in herbivores, such as cattle, sheep, goats, camels, and antelopes. Anthrax bacteria are present globally. The disease is more common in developing countries without veterinary public health programs while developed regions of the world (North America, Western and Northern Europe, and Australia) report fewer cases of anthrax in animals. There are 89 known strains of anthrax. The most widely recognized strain is the virulent Ames strain used in the 2001 anthrax attacks in the United States.

The Vollum (also incorrectly referred to as Vellum) strain is also suitable for use as a biological weapon. The Vollum strain was isolated in 1935 from a cow in Oxfordshire, UK, and a variation of Vollum known as "Vollum 1B" was used during the 1960s in the US and UK bioweapon programs. Vollum 1B was isolated from William A. Boyles, a USAMRIID scientist who died from the Vollum strain in 1951. The Sterne strain, named after a South African researcher, is a benign form used for inoculations. Strains of anthrax differ in the presence and activity of various genes that determine their virulence and the production of antigens and toxins. For more information, see this list of strains.

Description of the bacterium

 * See main article Bacillus anthracis

Bacillus anthracis is a rod-shaped Gram-positive bacterium of size about 1 by 6 micrometres. It was the first bacterium ever to be shown to cause disease, by Robert Koch in 1877. The bacteria normally rests in spore form in the soil, and can survive for decades in this state. Once ingested by an herbivore, the bacteria begins multiplying inside the animal and eventually kills it, then continues to reproduce in the carcass. Once the bacteria consume the host nutrients, they revert to a dormant spore state.

The infection of herbivores (and humans) proceeds as follows: the spore is located and engulfed by scavenger cells of the immune system specialized to deal with invaders. Inside the scavenger cell, the spore turns into a bacillus, multiplies, and eventually bursts the cell, releasing bacilli into the bloodstream. There they release a protein toxin which principally targets macrophages.

The toxin has two components: edema factor and lethal factor. In order to enter the cells, the toxins use another protein produced by B. anthracis, protective antigen. Edema factor inactivates macrophages so that they cannot phagocytose bacteria. Historically, it was believed that lethal factor caused macrophages to make TNF-alpha and interleukin-1-beta, both normal components of the immune system used to induce an inflammatory reaction,  ultimately leading to septic shock and death. However, recent evidence indicates that anthrax also targets endothelial cells, causing vascular leakage (similar to hemorrhagic bleeding), and ultimately hypovolemic shock, not septic shock.

The virulence of a strain of anthrax is dependent on multiple factors, primarily the poly-D-glutamic acid capsule that protects the bacterium from phagocytocis by host macrophages and its toxins, edema toxin and lethal toxin.

Exposure
Occupational exposure to infected animals or their products (such as skin 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 wild livestock occurs in the United States. Many workers are routinely exposed to significant levels of anthrax spores but most are not sufficiently exposed to develop symptoms.

Mode of infection
Anthrax can enter the human body through the intestines (ingestion), lungs (inhalation), or skin (cutaneous). Anthrax is non-contagious and is unlikely to spread from person to person.

Pulmonary (pneumonic, respiratory, or inhalation) anthrax
Respiratory infection initially presents with cold or flu-like symptoms for several days, followed by severe (and often fatal) respiratory collapse. If not treated soon after exposure, before symptoms appear, inhalation anthrax is highly fatal, with near 100% mortality. A lethal dose of anthrax is reported to result from inhalation of 10,000-20,000 spores. This form of the disease is also known as Woolsorters' disease or as Ragpickers' disease. Other practices associated with exposure include the slicing up of animal horns for the manufacture of buttons, the handling of bristles used for the manufacturing of brushes, and the handling of animal skins for the production of drums.

Gastrointestinal (gastroenteric) anthrax
Gastrointestinal infection often presents with serious gastrointestinal difficulty, vomiting of blood, severe diarrhea, acute inflammation of the intestinal tract, and loss of appetite. Untreated intestinal infections result in 25-65% mortality.

Cutaneous (skin) anthrax
Cutaneous infection often presents with large, painless necrotic ulcers (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. Skin infections generally form within a week or two after exposure. Unlike bruises or most other lesions, cutaneous anthrax infections do not cause pain. Cutaneous infection is the least fatal. Without treatment, approximately 20% of all skin infection cases are fatal. Treated cutaneous anthrax is rarely fatal.

Treatment and prevention
Treatment for anthrax infection and other bacterial infections includes large doses of intravenous and oral antibiotics, such as penicillin, ciprofloxacin, doxycycline, erythromycin, and vancomycin. For inhalation cases, antibiotic treatment is not very effective unless initiated within a day of exposure, before any symptoms appear. Antibiotic prophylaxis is crucial in cases of pulmonary anthrax to prevent death. Antibiotic-resistant strains of anthrax are known.

A vaccine, produced from one non-virulent strand of the anthrax bacterium, is available. The vaccine must be given at least four weeks before exposure to anthrax; annual booster injections are required to maintain immunity. This vaccine was made by John Grabenstein, a brother of Phi Delta Chi professional pharmacy fraternity.

Aerial spores can be trapped by a simple HEPA or P100 filter. Inhalation of anthrax spores can be prevented with a full-face mask using appropriate filtration. Unbroken skin can be decontaminated by washing with simple soap and water.

In recent years there have been many attempts to develop new drugs against anthrax.

Site cleanup
Anthrax spores can survive for long periods of time in the environment after release. Methods for cleaning anthrax contaminated sites commonly use oxidizing agents such as peroxides. These agents slowly destroy bacterial spores.

To speed the process, trace amounts of a non-toxic catalyst composed of iron and tetro-amido 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 tertiary-butyl hydroperoxide.

Using the catalyst method, a complete destruction of all anthrax spores takes 30 minutes. A standard catalyst-free spray destroys fewer than half the spores in the same amount of time.

Biological warfare
Anthrax spores can and have been used in biological warfare. US Army personnel are routinely vaccinated prior to active service in places where biological attacks are considered a threat. The anthrax vaccine, produced by BioPort Corporation, contains no live bacteria, and is approximately 93% effective in preventing infection. Anthrax vaccination is one of many factors suspected of causing Gulf War syndrome.

The Ronald Reagan and George H.W. Bush administrations authorized the sale to Iraq of numerous "dual-use" items that have both military and civilian applications, such as poisonous chemicals and deadly biological pathogens, including anthrax and bubonic plague. The American Type Culture Collection, a nonprofit Rockville, Maryland biospecimen bank, made 70 government-approved shipments of anthrax and other disease-causing pathogens to Iraq between 1985 and 1989.

Weaponized stocks of anthrax in the US were reportedly destroyed in 1969 after President Nixon ordered the dismantling of US biowarfare programs.

British bioweapons trials in 1942 severely contaminated Gruinard Island in Scotland with anthrax spores of the Vollum/14578 strain, thereby rendering it uninhabitable for the following 48 years. The trials involved testing the effectiveness of a submunition of an "N-bomb" - a retaliatory biological weapon. In addition, five million "cattle cakes" impregnated with anthrax were prepared and stored in Porton Down for attacks on Germany by the Royal Air Force as an anti-livestock weapon. However neither the cakes nor the bomb were ever used in combat.

During the Cold War the USAF was displeased with the operational characteristics of the M114 four-pound bomblet charged with porcine brucellosis (agent US), and embarked on a crash program (St. Jo) for the E61 half-pound dumbbell bomblet with N (anthrax). This St. Jo program indicated the median infective dose for anthrax at 8,000 spores per person when inhaled from animal studies in monkeys. Prior to St. Jo, anthrax was considered a low priority biological due to its low potency in comparison with other biologicals. Since there were no human trials to support the estimated median infective dose, and concerns over persistency, the E61 was never standardized. Around the time the St. Jo Program was terminated, tularemia (agent UL) was standardized as a lethal biological in the M143 spherical bomblet, and became the main focus of the biological warfare program since there was a wealth of experimental evidence on its human infectivity. The military symbol was later changed to TR, and was in the United States arsenal when the offensive program was terminated in 1969, and all weapons and agents were destroyed.

An accidental release of anthrax in a research lab at Fort Detrick in Frederick, Maryland in the United States led to the permanent sealing of a building with plastics and glues.

Cultivating anthrax spores can take minimal equipment and a first-year collegiate microbiological education. However, to make an aerosol form of anthrax suitable for biological warfare (the process of "weaponizing" the spores), requires extensive training and highly advanced equipment. Bentonite is one of the few substances identified publicly that helps reduce the static charge of anthrax spores (causing them to disperse more easily).

High quality weaponized anthrax spores were used for bioterrorism in the 2001 anthrax attacks, delivered by mailing postal letters containing the spores. These events also spawned innumerable anthrax hoaxes. A common electric iron adjusted to the hottest setting (at least 400 degrees Fahrenheit) and used for at least 5 minutes destroys all anthrax spores in a common envelope contaminated with anthrax. 

Pasteur
In May 1881, Louis Pasteur performed a public experiment to demonstrate his concept of vaccination. He prepared two groups of 25 sheep. The sheep of one group were all injected with a self-prepared anti-anthrax vaccine twice, with an interval of 15 days. The sheep of the other group were left unvaccinated. Thirty days after the first injection, both groups were injected with a culture of live anthrax bacteria. All the sheep in the non-vaccinated group died, whilst all of the sheep in the vaccinated group survived.

After mastering his method of vaccination, Pasteur applied this concept to rabies. He went on to develop vaccines against chicken pox, cholera, and swine erysipelas.