What is Anthrax?
Anthrax is a disease caused by the rod-shaped bacterium Bacillus anthracis, an endospore forming gram positive rod bacterium. The disease is also known as Woolsorters' disease, ragpickers' disease and charbon. It is primarily found in hoofed animals with hides, such as goats, sheep, cattle and horses. Anthrax is found worldwide, although many Western countries have nearly eliminated the disease by vaccinating animals against the disease. The disease is spread to man by contact, on open wounds or internal membranes, with infected animal hides or meat . It is not spread from person to person by respiratory means, unlike many viruses. Usually humans acquire the disease by skin contact with the bacteria or by inhaling the bacterial spores found in sheep's wool. The bacterium forms hard-shelled endospores that may go into a kind of hibernation. The spore allows the anthrax bacterium to remain in a dormant state for years protected against the environment and to become reactivated when transferred to a favorable growth medium, such as a human or animal. These spores are very hardy being resistant to sunlight, heat and disinfectant. They have been known to survive in soil for 80 years.
The real illness and death caused by anthrax is the done by the toxins produced by bacteria. Toxins are produced when the spore is in a favorable environment. The toxin has three components named the edema factor, the protective antigen, and the lethal factor. An excellent review of the subject is found in the September 9, 1999 issue of the New England Journal of Medicine titled Medical Progress: Anthrax (New England Journal of Medicine).
How do you catch anthrax?
You can contract anthrax by inhaling a lot of spores (at least 8,000 to 10,000), by eating contaminated meat or by coming into contact with the bacterium through an open wound. The same bug causes all three forms of the disease, but anthrax caused by inhaling is by far the most dangerous.
Is anthrax contagious?
Rarely. Transmission requires direct contact with the spores. Even people who get inhalation anthrax do not exhale spores.
Is Anthrax a biological warfare agent?
Yes. As an agent of biological warfare, it is suspected that a cloud of Anthrax spores would be released at a strategic location to be inhaled by the people under attack. As such, the symptoms of Anthrax encountered in warfare would mimic those expected for inhalation of anthrax spores, as opposed to those expected for skin contact or ingestion of the bacteria.
Is Anthrax a bioterrorism agent?
If somebody sent me anthrax in a letter or package, would I be able to see it?
Generally, yes. For anthrax spores to be used as a weapon, they need to be dried and processed into a stable, powder-like form that will disperse in the air. The most refined bacterial spores form a fine, white dust. Cruder preparations have a brownish tint and are heavier; these spores tend to clump together and drop to the ground, making them less effective terror weapons.
Is anthrax treatable?
Yes, to varying degrees. Contact and ingested forms respond best to treatment, with many of the antibiotics currently on the market--penicillin, tetracycline, doxycycline and fluoroquinolones such as Levaquin and Cipro. Cipro gets the most press because it is the only one specifically approved by the Food and Drug Administration (FDA) to treat anthrax. But unless you are exposed to one of the strains genetically engineered to be resistant to other antibiotics, you don't need Cipro. Inhalation cases can be treated with the same antibiotics if treatment is begun soon after infection.
Can I get vaccinated against anthrax?
No. BioPort, the only manufacturer licensed by the FDA to make an anthrax vaccine, has stopped shipments because its facility did not meet FDA standards. BioPort began renovating its plant in 1999 and expects to begin filling orders again by the end of the year. The company's vaccine is available only to military, laboratory personnel, and farmers who shear sheep for a living. It is not 100% effective. It can also have serious side effects. Without a real and present danger of a widespread anthrax attack, health experts believe it would be counterproductive to vaccinate the U.S. population.
Should I start taking antibiotics to protect myself?
No, because taking antibiotics without an active infection--or taking too short a course of antibiotics--only opens the door for bacteria to become resistant, rendering the medications ineffective. In addition, physicians should not be prescribing Cipro so people can stockpile the drug. Shortages could occur, and patients with legitimate, urgent medical need for the antibiotic would not be able to get the pills.
Should I get tested for anthrax if I have a fever and flulike symptoms?
No; unless you have been exposed to a known anthraz source. Most health-care personnel at local hospitals are able to conduct the proper tests to detect Bacillus anthracis. If you are worried, it makes sense to get tested, but odds are that you have not been exposed to anthrax. If you have flu symptoms, you probably have the flu.
What is Anthrax?
About 1-6 days after inhaling Bacillus anthracis spores there would be a gradual onset of vague symptoms of illness such as fatigue, fever, mild discomfort in the chest and a possibly a dry cough. The symptoms would improve for a few hours or 2-3 days. Then, there would be sudden onset of difficulty in breathing, profuse sweating, cyanosis (blue colored skin), shock and death in 24-36 hours.
These symptoms are essentially those of Woolsorter's disease, which is caused by inhalation of Bacillus anthracis spores rather than contact with the bacterium through the skin. Contact through the skin is the most common "naturally" occurring form of Anthrax and is characterized by swelling and boils on the skin. Skin symptoms would not necessarily be expected with Anthrax resulting from inhaled spores in BW
History of Anthrax
Anthrax has been reported and described since ancient times by Hindus, Greeks and Romans. The association of infection in man (intestinal form) with eating the meat of infected animals was reported in pre-Christian writings. The first US outbreak of anthrax was reported in Kentucky in 1824. The Bacillus anthracis bacterium was discovered in sheep in 1850.
Robert Koch was born on December 11, 1843, at Clausthal in the Upper Harz Mountains. The son of a mining engineer, he astounded his parents at the age of five by telling them that he had, with the aid of the newspapers, taught himself to read, a feat which foreshadowed the intelligence and methodical persistence which were to be so characteristic of him in later life. He attended the local high school («Gymnasium») and there showed an interest in biology and, like his father, a strong urge to travel.
In 1862 Koch went to the University of Göttingen to study medicine. Here the Professor of Anatomy was Jacob Henle and Koch was, no doubt, influenced by Henle's view, published in 1840, that infectious diseases were caused by living, parasitic organisms. After taking his M.D. degree in 1866, Koch went to Berlin for six months of chemical study and there came under the influence of Virchow. In 1867 he settled, after a period as Assistant in the General Hospital at Hamburg, in general practice, first at Langenhagen and soon after, in 1869, at Rackwitz, in the Province of Posen. Here he passed his District Medical Officer's Examination. In 1870 he volunteered for service in the Franco-Prussian war and from 1872 to 1880 he was District Medical Officer for Wollstein. It was here that he carried out the epoch-making researches which placed him at one step in the front rank of scientific workers.
Anthrax was, at that time, prevalent among the farm animals in the Wollstein district and Koch, although he had no scientific equipment and was cut off entirely from libraries and contact with other scientific workers, embarked, in spite of the demands made on him by his busy practice, on a study of this disease. His laboratory was the 4-roomed flat that was his home, and his equipment, apart from the microscope given to him by his wife, he provided for himself. Earlier the anthrax bacillus had been discovered by Pollender, Rayer and Davaine, and Koch set himself to prove scientifically that this bacillus is, in fact, the cause of the disease. He inoculated mice, by means of home-made slivers of wood, with anthrax bacilli taken from the spleens of farm animals that had died of anthrax, and found that these mice were all killed by the bacilli, whereas mice inoculated at the same time with blood from the spleens of healthy animals did not suffer from the disease. This confirmed the work of others who had shown that the disease can be transmitted by means of the blood of animals suffering from anthrax.
But this did not satisfy Koch. He also wanted to know whether anthrax bacilli that had never been in contact with any kind of animal could cause the disease. To solve this problem he obtained pure cultures of the bacilli by growing them on the aqueous humour of the ox's eye. By studying, drawing and photographing these cultures, Koch recorded the multiplication of the bacilli and noted that, when conditions are unfavourable to them, they produce inside themselves rounded spores which can resist adverse conditions, especially lack of oxygen and that, when suitable conditions of life are restored, the spores give rise to bacilli again. Koch grew the bacilli for several generations in these pure cultures and showed that, although they had had no contact with any kind of animal, they could stil1 cause anthrax.
Koch isolated the bacterium in 1877 and recovered it from experimentally infected animals. Louis Pasteur produced the first effective animal vaccine in 1881.
Human disease is primarily limited to those working with infected animals or individuals in third world countries exposed to infected, unvaccinated animals. Over 10,000 cases were reported in Zimbabwe from 1979 to 1985. Approximately 2000 cases occur annually worldwide. Only 224 cases of cutaneous anthrax were reported in the US in the fifty year period ending in 1994. Even more rare, only 18 human cases of the inhalation form were reported in the US this century.
Accidental and intentional releases of biological weaponized forms of anthrax have been reported recently. In 1979, at least 68 deaths and 79 cases due to accidental release and downwind contamination from a Soviet military biological weapons production facility in Sverdlovsk, Russia. For a complete description from an on scene investigator, see the book by Professor Jeanne Guillemin. There have been at least eight intentional releases of anthrax as a domestic bioterrorism agent by the Japanese organization, Aum Shinriyko, although no deaths or infections have been reported. There have been seven alleged threats or uses of anthrax in the US in the last two months of 1998 reported to the Centers for Disease Control. The CDC published "Interim Guidelines for Management of Domestic Bioterrorism Alleging use of Anthrax" in the Feb 5, 1999 issue of Morbidity and Mortality Weekly Report.
For comprehensive resources on bioterrorism, the St. Louis University School of Public Health's Center for the Study of Bioterrorism and Emerging Infections. A commentary in Aviation Week and Space Technology by former Senator Sam Nunn addresses the threat of bioterrorism in the US. Medscape, a resource for physicianns that requires free registration, has posted a resource for bioterrorism with dozens of articles and news links that are updated regularly.
Recommendations for preventing anthrax in "at-risk" individuals focus on pre-exposure vaccination. Treatment for the disease is based on successful early identification, use of antibiotics and post-exposure vaccination.
(source CNN) Although it's surfacing anew as a terrorist weapon, the deadly anthrax disease has plagued the world for centuries, with reports of it dating back to biblical times.
Anthrax is blamed for several devastating plagues that killed both humans and livestock. Soon after scientists learned more about it in the late 1800s, it emerged in World War I as a biological weapon.
Several countries, including Germany, Japan, the United States, the United Kingdom, Iraq and the former Soviet Union, are believed to have experimented with anthrax, but its use in warfare has been limited.
1500 B.C. -- Fifth Egyptian plague, affecting livestock, and the sixth, known as the plague of boils, symptomatic of anthrax
1600s -- "Black Bane," thought to be anthrax, kills 60,000 cattle in Europe
1876 -- Robert Koch confirms bacterial origin of anthrax
1880 -- First successful immunization of livestock against anthrax .
1915 -- German agents in the United States believed to have injected horses, mules, and cattle with anthrax on their way to Europe during World War I
1937 -- Japan starts biological warfare program in Manchuria, including tests involving anthrax
1942 -- United Kingdom experiments with anthrax at Gruinard Island off the coast of Scotland. It was only recently decontaminated.
1943 -- United States begins developing anthrax weapons
1945 -- Anthrax outbreak in Iran kills 1 million sheep
1950s and '60s -- U.S. biological warfare program continues after World War II at Fort Detrick, Maryland
1969 -- President Richard Nixon ends United States' offensive biological weapons program. Defensive work continues
1970 -- Anthrax vaccine approved by U.S. Food and Drug Administration
1972 -- International convention outlaws development or stockpiling of biological weapons
1978-80 -- Human anthrax epidemic strikes Zimbabwe, infecting more than 6,000 and killing as many as 100
1979 -- Aerosolized anthrax spores released accidentally at a Soviet Union military facility, killing about 68 people
1991 -- U.S. troops vaccinated for anthrax in preparation for Gulf War
1990-93 -- The terrorist group, Aum Shinrikyo, releases anthrax in Tokyo but no one is injured
1995 -- Iraq admits it produced 8,500 liters of concentrated anthrax as part of biological weapons program
1998 -- U.S. Secretary of Defense William Cohen approves anthrax vaccination plan for all military service members
2001 -- Letters containing anthrax spores are mailed to media services one week after the September 11 terrorist attacks on the Pentagon and World Trade Center. It was the first of a number of incidents around the country. In Florida, a man dies after inhaling anthrax at the offices of American Media Inc. and two postal workers in Washington, D.C. dies from inhalation anthrax
Forms of Anthrax: The forms and symptoms of anthrax are discussed in the sections below.
Three forms of the disease exist in man. The cutaneous (skin) form is the most common among workers contacting infected animals with entry through cuts or scrapes in the skin. This group of people also were the subjects for testing the safety and efficacy of the vaccine in humans because of their high risk occupation. The primary symptom is a deep, black, slow-healing, painless ulcer. With treatment with antibiotics or the anthrax vaccine is prompt, survival rates are excellent. Untreated cutaneous anthrax has a 15-20% fatality rate.
The intestinal (stomach) form is caused by eating undercooked meat from infected animals and is more common in underdeveloped countries. Symptoms include nausea, bloody vomiting and diarrhea. Estimates of untreated fatality rates range from 25-90%. Fatality rates with treatment may still reach 20%.
The inhalation form is caused by breathing anthrax spores which settle in the lung and reactivate in the favorable environment of the body. It is a rare form of the disease, but is the primary form of this disease used in biological warfare and domestic bioterrorism weapons. Symptoms usually start as a cough and fever over one to two days, but rapidly progress to respiratory failure, shock and death. Because of the difficulty in recognizing and quickly diagnosing the disease, delay in treatment of unprotected individuals has very low survival rates. Previous exposure to anthrax or the vaccine confers some degree of immunity.
Disinfection of bacterial contaminated articles may be accomplished using a 0.05% hypochlorite solution (1 tbps. household chlorine bleach per gallon of water). Spore destruction requires steam sterilization.
The military chemical protective mask is effective against inhalation of all Biological Warfare Agents.
Treatment of infected individuals
Cipro, or ciprofloxacin HCl, is an oral antibiotic that was, until recently, used primarily to combat urinary tract infections. In the summer of 2000, after hearing testimony on bioterrorist threats, rattled lawmakers launched an investigation into U.S. preparedness. The medical community suggested that two drugs were feasible treatments for anthrax: Penicillin and doxycycline. And they found problems with both. Scientists fear that introducing massive amounts of penicillin into the general population could hasten the creation of mutant penicillin-resistant strains of bacteria. Likewise, there was some evidence that terrorists had engineered strains of the anthrax bacteria resistant to both penicillin and doxycylcines. There was another option, lawmakers were told: Cipro.
Bayer was notified, and members of Congress urged the Food and Drug Administration to speed up the often labored process of drug approval. In August 2000, Cipro, which had demonstrated an anti-anthrax efficacy in tests on monkeys, was rushed through the approval process and dubbed the unequivocal drug of choice in the anthrax battle. It is currently the only drug used to treat inhalational (pulmonary) anthrax.
Bayer has patent rights over Cipro for at least another year — although those rights may now be challenged. In October of 2001, U.S. Senator Chuck Schumer of New York announced there is a section of federal law allowing the government to buy generic versions of patented drugs. If his proposal is approved, Schumer says, the public would not have to worry about buying Cipro, because the government would have a supply large enough to go around. In October of 2001 the Canadian government removed all of Bayer's patent rights for that country allowing the manufacture of generic versions.n
Health and government officials, alarmed by recent stockpiling of the drug due to the Anthrax bioterrorism attacks, eagerly point out that exposure to anthrax is still contained to an infinitesimally small portion of the population. They also warn there are dangers to self-medication, ranging from common side effects like nausea to the worst-case scenario: Cipro-resistant strains of the anthrax bacteria.
Experts say a bioattack takes sophisticated science.
Anthrax bacteria can be obtained from infected livestock or U.S. labs -- but only under highly restrictive conditions. Since the mid- to late 1990s, it became next to impossible to acquire the bacteria in the United States: Because of concerns that Iraq was producing anthrax weapons, U.S. authorities clamped down on the sale of anthrax bacteria. In the 1980s, Iraq obtained anthrax strains from the American Type Culture Collection, a Maryland supplier of biological products to the scientific community. It is also possible that terrorists could obtain the bacteria from foreign labs, governments that support terrorism or former Soviet scientists.
Of all biological agents that could be used in biological weapons, anthrax is not the deadliest and it is difficult to harness and deliver. For anthrax to kill hundreds of thousands of people bacterial spores must be of the most virulent strain, cannot exceed a certain microscopic size (1 to 5 microns is optimal) and must be delivered in a perfectly cultured aerosol form in ideal weather conditions -- a clear night with no more than a light wind. If these conditions are not met, the experts say, the anthrax bacteria likely will either die or dissipate in the winds without affecting large numbers of people.
It is possible to deliver anthrax in powder form attached to or enclosed in envelopes or packages, but it is only effective if the recipient shakes the container.
The expertise needed to turn the anthrax spores into a dry powder, able to survive for days in the mail or on somebody's desk, would have to be so sophisticated as to require involvement by a government or military organization, not individuals.
The consensus of experts on bioterrorism is that a terrorist or criminal group would most likely seek to deliver anthrax spores in aerosol form, either from a spray bottle, a land vehicle or a crop-dusting plane. But the delivery mechanism must be perfect and the atmospheric conditions quite stable.
A successful infection rate requires that people inhale between 8,000 and 10,000 spores, and then only 50 percent have a chance of developing the disease.
The recent postal-bioterrorism attacks on the media seems to be a deliberate exposure, but not necessarily a targeted attack designed to kill large numbers of people.
Weaponized Anthrax Modified for Vaccine Resistance
The major concern is whether weaponized forms of anthrax bacteria will be modified to decrease the effectiveness of known vaccines. Some reports of attempts to modify the type of anthrax weaponized have come from defectors from hostile countries. According to Dr. Kenneth Todar of the University of Wisconsin-Madison, fatal anthrax disease is only caused by the simultaneous presence of all three toxin protein factors (see above). The current vaccine produces antibodies to one of the factors, the Protective Antigen. To render the vaccine ineffective, the modified weaponized form would have to produce disease without the Protective Antigen. It would be much easier to modify anthrax to be resistant against several of the antibiotics used to treat the disease in victims than it would be to render the vaccine ineffective.
Defectors from the former Soviet Union biological weapons program have indicated that the Soviets were trying to modify a weaponizable form of anthrax that may be resistant to the current
anthrax vaccine. Reportedly, attempts at fully weaponizing thealtered strains have been unsuccessful. Nonetheless, on September 4, 2001, the
US announced it was attempting to duplicate the modified Russian strain. The purpose of this attempt is to
determine if the current anthrax vaccine available in the US provides adequate protection against the strain. If not, new vaccines will have to be designed and produced to provide full
protection. Ironically, persons at risk may have to receive two vaccines to protect against modified and traditional strains.
What is the Anthrax Vaccine?
The anthrax vaccine is an inactivated (killed), cell-free filtrate type vaccine. The vaccine stimulates immunity by triggering antibodies to one of the three toxic protein factors associated with the anthrax bacterium. This antibody stimulation is caused by the Protective Antigen in the vaccine derived from the culture filtrate of an avirulent (non-disease causing) strain of B. anthracis. It is not possible to contract anthrax from the vaccine. Live, attenuated viral vaccines, such as rubella, can cause disease.
The vaccine uses aluminum hydroxide as an adjuvant to boost the immunogenicity effect. Preservatives are 0.02% formaldehyde and 0.0025% benzethonium chloride. These components are used in many of the vaccines used routinely worldwide.
The vaccine was first researched on animal mill workers in the US in the 1950's. The studies concluded that the vaccine was 92% efficacious. The study by Brachman published in 1962 is considered the first comprehensive study in humans. The Centers for Disease Control (CDC) submitted an Investigational New Drug request for the licensing of the vaccine in April 1966. The Michigan Department of Public Health produced the vaccine. 16,000 doses of the vaccine were given to 7,000 individuals under the protocol approved by the Division of Biologics Standards of the National Institutes of Health. Rates of adverse reactions were documented and compared favorably to other vaccines approved for human use. Because of the small portion of the population at risk and relatively small number of vaccines given, anthrax vaccine studies are not as robust as those vaccines for much more common diseases administered to very large numbers of people over extended periods of time. Therefore, it is difficult for scientific studies of the effectiveness of the anthrax vaccine to achieve "statistical significance" or firm conclusions based on smaller numbers studied.
In November 1970, the Division of Biologics Standards (NIH) approved the vaccine for human use in the United States. This approval function is now housed in the Center for Biologics Evaluation and Research under the Food and Drug Administration. The Michigan Department of Public Health production facility changed its name to the Michigan Biological Products Institute in 1996. The production facility was bought by BioPort corporation in September 1998. This facility is the sole source manufacturer for the approved human anthrax vaccine in the US and is presently not approved for production.
The FDA approved schedule for the vaccine includes six doses in the primary series. The first three doses are given at two week intervals followed by three doses at six month intervals from the initial vaccination. Annual vaccines are then required to maintain high levels of immunity. Approximately 68,000 doses were given to civilians, mostly veterinarians, from 1970 to 1989. The initial mass immunization of the military began during Operation Desert Shield when over a quarter of a million doses were administered to approximately 150,000 people, but exact numbers of individuals immunized and number of doses per individual are not known due to administrative lapses. Since 1998, over 1.98 million doses have been given.
Effectiveness of the vaccine in Protecting Against Pulmonary Anthrax
A second area of concern is the lack of robust research demonstrating the effectiveness of the vaccine in preventing the inhalation form of anthrax. The initial study of the anthrax vaccine by Brachman in 1962 demonstrated that vaccinated mill workers had 92.5% fewer infections than unvaccinated workers. No cases of inhalation anthrax occurred among the vaccinated group, but five cases of inhaled anthrax occurred in the unvaccinated group. The difference between zero and five involved too few people to be considered statistically conclusive, although a trend is apparent.
More recently, 44 of 45 Rhesus monkeys given one or two doses of the vaccine survived inhalational challenges of up to 900 times the lethal dose of anthrax spores. The one monkey that died occurred two years after the last dose of vaccine, but had survived earlier challenges. DOD researchers consider the Rhesus monkey on inhalational anthrax the closest model to the human because of the similar pathological findings in the anthrax infected lungs of man and monkeys. All unvaccinated monkeys exposed to similar challenges died from pulmonary anthrax.
Studies in guinea pigs and mice have not shown high rates of protection offered by the vaccine. Pathological findings of anthrax disease in these non-primate animals vary from that of man and monkeys. The route of administration in these non-primate studies has not generally been inhalation, the likely route of the weaponized form. It is impossible to predict how much of a dose of anthrax a soldier would be exposed to if used as a weapon. Factors including proximity to the explosion, wind direction, use of a chemical-biological defense mask and concentration of weapon would all be factors. Further research is not ethical nor likely, so the question probably will never be answered with controlled studies.
Other organisms that may be used in bioterrorism
Germs of Terror (USNWR 28 Oct 2001, page 44)