Anthrax

For other uses, see Anthrax (disambiguation).

Anthrax
Specialty	Infectious diseases, veterinary medicine

Anthrax' is an acute infectious disease in humans and animals that is caused by the bacterium Bacillus anthracis and is highly lethal in some forms. Anthrax is one of only a few bacteria that can form long lived spores. When the bacteria’s life cycle is threatened by factors such as lack of food caused by their host dying or change of temperature, the bacteria turn themselves into more or less dormant spores to wait for another host to continue their life cycle. On breathing, ingesting or getting anthrax spores in a cut in the skin these spores reactivate themselves and multiply in their new host very rapidly. The anthrax spores in the soil are very tough and can live many decades and perhaps centuries and are known to occur on all continents except Antarctica. Anthrax most commonly occurs in wild and domestic grass eating mammals (ruminants) who ingest or breathe in the spores while eating grass. Anthrax can also be caught by humans when they are exposed to dead infected animals, eat tissue from infected animals, or are exposed to a high density of anthrax spores from an animals fur, hide, or wool. Anthrax spores can be grown outside the body and used as a biological weapon. Anthrax cannot spread directly from human to human; but anthrax spores can be transported by human clothing , shoes etc. and if a person dies of anthrax their body can be a very dangerous source of anthrax spores. The word anthrax is derived from the Greek word anthrakis, or "coal", in reference to the black skin lesions victims develop in a cutaneous skin infection.

Overview

Anthrax bacteria.

Anthrax is one of the oldest recorded diseases of grazing animals like sheep and cattle and is believed to be the Sixth Plague mentioned in the Book of Exodus in the Bible and by the Greek and Roman authors Homer’s Iliad, Virgil’s Georgics and Hippocrates writings. Anthrax can also infect humans, usually as the result of coming into contact with infected animal hides, fur, wool, leather or contaminated soil. Anthrax ("siberian ulcer" ) is now fairly rare (a few to no cases per year in the developed world) in humans although it still occasionally occurs in ruminants, such as cattle, sheep, goats, camels, wild buffalo, and antelopes.

Bacillus anthracis bacteria spores are soil-borne and because of their long lifetime they are still present globally and at animal burial sites of anthrax killed animals for many decades. Before the last century anthrax infections were a source of many thousands of dead animals and thousands of people dying each year in Europe, Asia and North America. [[1]] The great French scientist Louis Pasteur developed the first effective vaccine for anthrax in 1881. [2] Thanks to over a century of animal vaccination programs, sterilization of raw animal waste materials and anthrax eradication programs in North America, Australia, New Zealand, Russia, Europe and parts of Africa and Asia anthrax infection is now rare in domestic animals with normally only a few dozen cases reported every year. Anthrax is even rarer in (dogs and cats) where there is only one documented case in the USA in the last 15 years. Anthrax outbreaks do occur in a few wild animal populations with some regularity. [3] The disease is more common in developing countries without widespread veterinary or human public health programs.

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 developed but never used as a biological weapon during the Second World War. The Vollum (also incorrectly referred to as Vellum) strain was isolated in 1935 from a cow in Oxfordshire, UK. This is the same strain that was used during the Gruinard bioweapons trials. 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 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.

Description of the bacterium

Main article: Bacillus anthracis

Bacillus anthracis is a rod-shaped Gram-positive bacterium, about 1 by 9 micrometers in size. It was shown to cause disease by Robert Koch in 1877. [4] The bacterium normally rests in endospore form in the soil, and can survive for decades in this state. Once ingested by a ruminant or placed in an open cut, the bacterium begins multiplying inside the animal or human and in a few days to a month kills it. Veterinarians can often tell a possible anthrax induced death by its sudden occurrence and by the blood and bloody fluids that oozed from the body orifices. Most anthrax bacteria inside the body are destroyed by anaerobic bacteria that can grow without oxygen. The greater danger lies in the bodily fluids and blood that spills from the body and spill into the soil where the anthrax bacteria turn into a dormant protective spore form. Once formed the spores are devilishly hard to eradicate.

The infection of ruminants (and occasionally humans) normally proceeds as follows: 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 glands (lymph nodes) in the central chest cavity (mediastinum). Damage caused by the anthrax spores and bacilli to the central chest cavity lungs can cause chest pain and difficulty breathing. Once in the lymph glands, the spores germinate into active bacillus, that multiplies, and eventually bursts the macrophage cell, releasing many more bacilli into the bloodstream which are transferred to the entire body. Once in the blood stream these bacilli release a tripartite toxin (composed of lethal factor, edema factor and protective antigen) which is known to be the primary agents of tissue destruction, bleeding, and death. If antibiotics are given too late, even if the antibiotics eradicate the bacteria, some people still will die because the toxins produced by the bacilli still remain in their system at lethal dose levels.

In order to enter the cells, the toxins use another protein produced by B. anthracis, protective antigen. Edema factor inactivates neutrophils (a type of phagocytic cell) 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 (cells that lines serous cavities, lymph vessels, and blood vessels), causing vascular leakage (similar to hemorrhagic bleeding), and ultimately hypovolemic shock (low blood volume), and not only septic shock. In other words the patient bleeds to death internally.

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 neutrophils and its toxins, edema toxin and lethal toxin.

Exposure

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 exposures are not sufficient to develop anthrax infections. Presumably, the body’s natural defenses can destroy low levels of exposure. These people usually contract cutaneous anthrax if they catch anything. Historically, the most dangerous form of inhalation anthrax was called Woolsorters' disease because it was an occupational hazard for people who sorted wool. Fortunately this is now a very rare form of infection because of the much reduced incidence of anthrax disease in animals. The last fatal case of natural inhalation anthrax in the United States occurred in California in 1976, when a home weaver died after working with infected wool imported from Pakistan. The autopsy was done at UCLA hospital. 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. The details of this case have been described in a medical journal Human Pathology (Volume 9, pages 594-597, September, 1978).

In July 2006 an artist who worked with untreated animal skins became the first person in more than 30 years to die in the United Kingdom from anthrax.

Mode of infection

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. An infected human will generally be quarantined. However, anthrax does not usually spread from an infected human to a noninfected human. But if the disease is fatal the person’s body and its mass of anthrax bacilli becomes a potential source of infection to others and special precautions should be used to prevent more contamination. Unfortunately inhalation anthrax if left untreated till obvious symptoms occur will usually result in death--treatment was started too late.

Anthrax is usually contracted by handling infected animals or their wool, germ warfare/terrorism or laboratory accidents.

Inhalational anthrax - Mediastinal widening

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 promptly soon after exposure, before symptoms appear, inhalational anthrax is highly fatal, with near 100% mortality. A lethal dose of anthrax is reported to result from inhalation of about 10,000–20,000 spores. [5] Like all diseases there is probably a wide variation to susceptibility with evidence that some people may die from much lower exposures. Fortunately there is little documented evidence to verify the exact or average number of spores need for infection. Inhalation anthrax is also known as Woolsorters' disease or as Ragpickers' disease since these people often caught it. Other practices associated with exposure include the slicing up of animal horns for the manufacture of buttons, the handling of hair bristles used for the manufacturing of brushes, and the handling of animal skins. Whether these animal skins came from animals that died of the disease or from animals that had simply laid on ground that had spores on it is unknown.

Gastrointestinal (gastroenteric) anthrax

Gastrointestinal infection is most often caused by eating anthrax infected meat and is characterized by serious gastrointestinal difficulty, vomiting of blood, severe diarrhea, acute inflammation of the intestinal tract, and loss of appetite. Gastrointestinal infections can be treated but usually result in fatality rates of 25% to 60%, depending upon how soon treatment commences.

Cutaneous (skin) anthrax

File:Milzbrand.jpg

Anthrax skin lesion.

Cutaneous (on the skin) anthrax infection shows up as a boil-like skin lesion that eventually forms an ulcer with a black center (i.e., eschar). The black eschar often shows up as a 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. Cutaneous infections generally form within the site of spore penetration within 2 to 5 days after exposure. Unlike bruises or most other lesions, cutaneous anthrax infections normally do not cause pain. Cutaneous infection is the least fatal form of anthrax infection if treated. But without treatment, approximately 20% of all cutaneous skin infection cases may progress to toxemia and death. Treated cutaneous anthrax is rarely fatal.

Treatment and prevention

Direct person-to-person spread of anthrax is extremely unlikely; but a patient’s clothing and body may be contaminated with anthrax spores. Effective decontamination of people can be accomplished by a thorough wash down with anti-microbe effective soap and water. Waste water should be treated with bleach or other anti-microbal agent. Effective decontamination of articles can be accomplished by boiling contaminated articles in water for 30 minutes or longer and using common disinfectants. Chlorine is effective in destroying spores and vegetative cells on surfaces. Burning clothing is also effective. After decontamination, there is no need to immunize, treat or isolate contacts of persons ill with anthrax unless they also were also exposed to the same source of infection . Early antibiotic treatment of anthrax is essential–delay seriously lessens chances for survival. Treatment for anthrax infection and other bacterial infections includes large doses of intravenous and oral antibiotics, such as fluoroquinolones, like ciprofloxacin (cipro), doxycycline, erythromycin, vancomycin or penicillin. In possible cases of inhalation anthrax exposure to unvaccinated personnel early antibiotic prophylaxis treatment is crucial to prevent possible death. If death occurs from anthrax the body should be isolated to prevent possible spread of anthrax germs. Burial does not kill anthrax spores.

Delays of only a few days may make the disease untreatable. Initial symptoms may resemble a common cold – sore throat, mild fever, muscle aches and malaise. After several days, the symptoms may progress to severe breathing problems and shock and ultimately death. Death can occur from about two days to a month after exposure with deaths apparently peaking at about 8 days after exposure. Antibiotic-resistant strains of anthrax are known.

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. All of these procedures do not kill the spores which are very hard to kill and require extensive treatment to eradicate them. Filters, clothes, etc. exposed to possible anthrax contaminated environments should be treated with chemicals or destroyed by fire to minimize the possibility of spreading the contamination. In recent years there have been many attempts to develop new drugs against anthrax; but the existing supply still works fine if treatment is started soon enough.

Prevention can also be accomplished through early detection. In response to the anthrax attacks of October, 2001 utilizing the United States Postal Service(USPS), the USPS has installed BioDetection Systems(BDS)in their large scale mail cancellation facilities. BDS response plans have been formulated by the USPS in conjunction with local responders including fire, police, hospitals and public health. Employees of these facilities have been educated on Anthrax, response actions and prophylactic medication. Because of the time delay inherent in getting final verification that anthrax has been used, prophylactic antibiotic use should be started to possibly exposed personnel as soon as possible.

Anthrax vaccines

An FDA-licensed vaccine, produced from one non-virulent strain of the anthrax bacterium, is manufactured by BioPort Corporation, subsidiary of Emergent BioSolutions. The trade name is BioThrax, although it is commonly called Anthrax Vaccine Adsorbed (AVA). It is administered in a six-dose primary series at 0,2,4 weeks and 6,12,18 months; annual booster injections are required thereafter to maintain immunity.

Unlike the West the Soviets developed and used live spore anthrax vaccines produced in Tiblsi Georgia. This is know as the STI vaccine and its serious side effects restrict its use to healthy adults.

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, ethylene Oxide, Sandia Foam [6], (available as Mold Control 500, distributed by Scott’s Liquid Gold) chlorine dioxide (used in Hart Senate office building), liquid bleach products contain sodium hypochlorite. These agents slowly destroy bacterial spores. A bleach solution for treating hard surfaces has been approved by the EPA [7] can be prepared by mixing one part bleach (5.25%-6.00%) to one part white vinegar to eight parts water. Bleach and vinegar must not be combined together directly, rather some water must first be added to the bleach (e.g., two cups water to one cup of bleach), then vinegar (e.g., one cup), and then the rest of the water (e.g., six cups). The pH of the solution should be tested with a paper test strip; and treated surfaces must remain in contact with the bleach solution for 60 minutes (repeated applications will be necessary to keep the surfaces wet).

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 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. “You can heat them, expose them to the harshest chemicals, and they do not easily die.

Cleanups at a Senate office building, several contaminated postal facilities and other U.S. government and private office buildings showed that decontamination is possible, but it is time-consuming and costly. Clearing the Senate office building of anthrax spores cost $27 million, according to the Government Accountability Office. Cleaning the Brentwood postal facility outside Washington cost $130 million and took 26 months. Since then newer and less costly methods have been developed. [8], [9]

History

Discovery

Robert Koch, a German physician and scientist, first identified the bacteria which caused the anthrax disease in 1877. His pioneering work in the late nineteenth century was one of the first demonstrations that diseases could be caused by microbes. In a groundbreaking series of experiments he uncovered the life cycle 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 were still held over spontaneous generation versus cell theory. Koch went on to study the mechanisms of other diseases and was awarded the 1905 Nobel Prize in Physiology or Medicine for his discovery of the bacteria causing tuberculosis. Koch is today recognized as one of history's most important biologists and a founder of modern bacteriology.

First vaccination

In May 1881, Louis Pasteur performed a public experiment to demonstrate his concept of vaccination. He prepared two groups of 25 sheep, one goat and several cows. The animals of one group were all injected with a self-prepared anti-anthrax vaccine twice, with an interval of 15 days. The animals 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 animals in the non-vaccinated group died, whilst all of the animals 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.

Biological warfare

Colin Powell holding a model vial of anthrax while giving a presentation to the United Nations Security Council.

Anthrax spores can and have been used as a biological warfare weapon. There is a long history of bioweapons research in this area. For example, in 1942 British bioweapons trials severely contaminated Gruinard Island in Scotland with anthrax spores of the Vollum-14578 strain, thereby rendering it uninhabitable for the following 48 years. The Gruinard trials involved testing the effectiveness of a submunition of an "N-bomb"—a biological weapon. Additionally, 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 .

More recently, the Rhodesian government used anthrax against cattle and humans in the period 1978–1979 during its war with black nationalists.

US Army and British Army personnel are routinely vaccinated against anthrax prior to active service in places where biological attacks are considered a threat. The anthrax vaccine, produced by BioPort Corporation, contains non-living bacteria, and is approximately 93% effective in preventing infection.

Weaponized stocks of anthrax in the US were destroyed in 1971–72 after President Nixon ordered the dismantling of US biowarfare programs in 1969 and the destruction of all existing stockpiles of bioweapons[10]. Research continues to this day in the United States on ways to counter act possible bioweapons attacks.

Despite signing the 1972 agreement to end bioweapon production the government of the Soviet Union had an active bio weapons program that included the production of hundreds of tons of weapons-grade anthrax after this period. On 2 April 1979 part of the over one million people living in Sverdlovsk (now called Ekaterinburg, Russia), roughly 850 miles east of Moscow were exposed to a accidental release of anthrax from a biological weapon’s complex located near there. The first victim died after four days; ten victims died in eight days at the peak of the deaths and the last victim died six weeks later. In all at least 94 people were infected and at least 68 of them died. Extensive cleanup, vaccinations and extensive medical interventions managed to save about 30 of the victims. Extensive cover-ups and destruction of records by the KGB continued from 1979 till 1992 when Russian President Boris Yeltsin finally admitted this anthrax accident. A combined Russian and United States team investigated this accident in 1992 as reported by Jeanne Guillemin in 1999 [11], [12]

There was a ceramics plant directly across the street from the bio facility (compound 19) and nearly all of the night shift workers at the ceramics plant 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 (Alibek, 1999). 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 that all stray dogs be shot and that people not have contact with sick animals. There was also a voluntary evacuation and anthrax vaccination program established for people from 18–55 (Meselson et al., 1994).

To support the story, Soviet medical and legal journals published articles about an outbreak in livestock that caused GI anthrax in people who consumed the meat and cutaneous anthrax in people who came into contact with the animals. All medical and public health records were confiscated by the KGB (Meselson et al., 1994). In addition to the medical problems that the outbreak caused, it also caused Western countries to be more suspicious of a covert Soviet Bioweapons program and to increase their surveillance of suspected sites. In 1986, the American government was allowed to investigate the matter and concluded that the exposure was from aerosol anthrax from a military weapons facility (Sternbach, 2002). In 1992, President Yeltsin admitted that he was "absolutely certain" that "rumors" about the Soviet Union violating the 1972 Bioweapons Treaty were true. The Russians, like the US and UK, agreed to submit information to the UN about their bioweapons programs but the Russian report omitted known facilities and never acknowledged their weapons program (Alibek, 1999).

Theoretically, cultivating anthrax spores can be done with minimal special equipment and a first-year collegiate microbiological education. Fortunately, there are many obstacles to over come to do this and doing this can be quite dangerous. 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. Only a few grams of material were used in these attacks and it is unknown if this material was produced by a single individual or by a state sponsored bio-weapons program. These events also spawned innumerable anthrax hoaxes. In response, the US Postal Service sterilized some of the mail using a process of gamma irradiation combined with the use of a unique & proprietary enzyme treatment formula supplied by Sipco Industries Ltd

A scientific experiment performed by a high school student (later published in The Journal of Medical Toxicology) suggested that a common electric iron adjusted to the hottest setting (at least 400 degrees Fahrenheit) and used for at least 5 minutes should destroy all anthrax spores in a common envelope contaminated with anthrax.

See also

• 2001 anthrax attacks
• Anthrax hoaxes
• Ames strain
• Sverdlovsk Anthrax leak
• Anthrax toxin
• Anthrax Detection Device
• Anthrax Vaccine
• Anthrax Vaccine Immunization Program, or AVIP: the program for vaccinating all members of the armed services in the United States.

References

• Alibek, K. Biohazard. New York, New York: Dell Publishing, 1999.
• "Bacillus anthracis and anthrax". Todar's Online Textbook of Bacteriology (University of Wisconsin-Madison Department of Bacteriology). Retrieved June 17. {{cite web}}: Check date values in: |accessdate= (help); Unknown parameter |accessyear= ignored (|access-date= suggested) (help)
• "Anthrax". CDC Division of Bacterial and Mycotic Diseases. Retrieved June 17. {{cite web}}: Check date values in: |accessdate= (help); Unknown parameter |accessyear= ignored (|access-date= suggested) (help)
• "Focus on anthrax". Nature.com. Retrieved June 17. {{cite web}}: Check date values in: |accessdate= (help); Unknown parameter |accessyear= ignored (|access-date= suggested) (help)
• Chanda, A., S. Ketan, and C.P. Horwitz. 2004. Fe-TAML catalysts: A safe way to decontaminate an anthrax simulant. Society of Environmental Journalists annual meeting. October 20–24. Pittsburgh.
• Meselson, M. et al. (1994). "The Sverdlovsk Outbreak of 1979". Science 266(5188) 1202–1208
• Sternbach, G. (2002). "The History of Anthrax". The Journal of Emergency Medicine 24(4) 463–467.

External links

• Anthrax - Comprehensive information from the Centers for Disease Control and Prevention (CDC)
• Bioterrorism Category A Agents - Information Resources
• Cutaneous Anthrax Images and Diagnosis Synopsis
• Anthrax Detection Device
• Article re. Fort Detrick and Vollum strain of Anthrax
• Exports of biological materials to Iraq: mentions Vollum strain and Gruinard Island
• [13]
• [14]