Preventing and Treating Anthrax
Chapter 3
Preventing and Treating Anthrax
In the past, anthrax was one of the major killers of domestic animals worldwide. Over the course of history, anthrax also caused many human deaths. The devastation wrought by this fearful affliction prompted scientists and doctors to develop methods to prevent and treat the disease.
Development and Use of Anthrax Vaccines for Animals
In 1863 the French scientist Casimir-Joseph Davaine isolated "rod-shaped organisms" from the bodies of animals that had died from anthrax. He also demonstrated that anthrax could be passed to healthy animals by injection of blood from infected creatures. In 1876 the German physician Robert Koch proved that the "rod-shaped organisms," which were Bacillus anthracis bacteria, caused anthrax. He also described the bacteria's life cycle. These scientific breakthroughs provided researchers with the information necessary to develop anthrax vaccines.
The first anthrax vaccine for animals contained live, but attenuated (weakened) Bacillus anthracis spores. The vaccine was developed in 1880 by William S. Greenfield at the Brown Animal Sanatory Institution in London. Shortly afterward, the well-known French scientist Louis Pasteur formulated a similar anthrax vaccine. Pasteur's live-spore vaccine was made from a strain of Bacillus anthracis that had lost some of its ability to form anthrax toxins. Thus, the anthrax bacteria in the vaccine were much less deadly than "normal" anthrax organisms.
Pasteur publicly tested his anthrax vaccine in Pouilly-le-Fort, France, in June 1881, in front of a large group of veterinarians, doctors, farmers, government officials, and reporters. After Pasteur proved that his vaccine shielded most livestock from anthrax, it was accepted for general use. Over the next fifty years the Pasteur anthrax vaccine was employed in many parts of the world to protect domestic animals from the dreaded plague. However, the Pasteur vaccine was not stable enough to be stored for long periods of time and caused serious side effects—sometimes even death—in some animals.
In 1937 the South African scientist Max Sterne developed an improved animal anthrax vaccine. Sterne's live-spore vaccine was made from a strain of Bacillus anthracis, called 34F, that could not form a capsule. This greatly reduced the bacteria's ability to infect animals. Sterne's vaccine, which was more stable and safer than Pasteur's vaccine, proved very effective. Hence, the Sterne vaccine—and vaccines derived from it—are used all over the world today.
For maximum protection animals must receive two injections of the Sterne vaccine, two weeks apart, followed by a yearly booster shot. Because the live-spore vaccine must germinate and grow in the vaccinated animal's body to provide protection, immunity takes from seven to fourteen days to develop. There, however, are some safety concerns associated with the Sterne vaccine. Inoculation may cause tissue damage at the site of injection, and some animals have died following inoculation.
By the late twentieth century routine vaccination had greatly reduced the incidence of animal anthrax, especially in developed countries. In the United States, for example, farmers and ranchers in spore-infected areas are advised to vaccinate, or revaccinate, their herds each year—preferably two to four weeks before "anthrax season" might be expected to begin. Konrad Eugster, executive director of the Texas Veterinary Medical Diagnostic Laboratory in College Station, advises: "If they are in an area where anthrax has been found or on a ranch that has had a case any time in the past thirty years, people should vaccinate their animals."13 Failure to vaccinate can cause severe losses. In west Texas, for instance, anthrax outbreaks have been known to kill high-priced bulls, worth three thousand dollars or more, in minutes. Therefore, ranchers in the region usually vaccinate their livestock each spring.
Animal owners are also advised to immunize their herds after natural disasters. Following floods in Minnesota in 2002, for example, Minnesota state veterinarian Bill Hartmann recommended: "If [animal producers] are going to graze on land that flooded, they should vaccinate their animals to prevent anthrax. The way I look at it, two dollars [the price of an anthrax vaccine dose] is cheap insurance for an animal that is worth more than a thousand dollars."14
Treating and Controlling Outbreaks of Animal Anthrax
If anthrax strikes an unvaccinated herd, state veterinarians advise owners to remove livestock from the contaminated area and to treat infected animals with antibiotics (substances that kill bacteria) such as penicillin, ciprofloxacin, or oxytetracycline for at least five days. This therapy can sometimes prevent death. Farmers and ranchers are also advised to vaccinate apparently healthy animals in the herd, as well as livestock in surrounding areas. Veterinarians caution animal owners, however, not to administer vaccine and antibiotics to an animal at the same time. The antibiotics, which work by killing bacteria, will also kill the live organisms in the vaccine, rendering it ineffective. In cases of peracute anthrax, which kills within hours, effective treatment with medicine or antibiotics is not possible.
Vaccines and antibiotics are rarely used to control anthrax in wild animals. For these creatures, medicines must be administered by darting (shooting medicine-laden darts), which is difficult and expensive. However, wildlife workers in the African nation of Tanzania reportedly used antibiotics to stop an anthrax outbreak among antelopes, saving fifty animals.
If an animal dies of anthrax, medical experts recommend that the creature's carcass be deeply buried or burned without delay. Terry Conger, a veterinarian and Texas's state epidemiologist for animal disease, favors burning. "Rather than fooling with the animal carcasses, it's highly recommended that [farmers] burn that animal on site," notes Conger. "If they bury the animal, that will only preserve the [anthrax] organism deep within the soil."15 If the carcass is buried, health authorities recommend covering it with crystalline quicklime, a powerful disinfectant. In addition, experts advise that potentially contaminated items such as food, water, bedding, blankets, fences, barns, and the soil and grass around the victim be destroyed or disinfected. Potent liquid disinfectants, approved by veterinarians, include Roccal-D, Nolvasan, and household bleach. To stop the spread of anthrax during an epidemic, farmers and ranchers are also advised to quarantine infected animals, control biting insects, and maintain good sanitation.
Promoting Anthrax Control in Developing Regions
Most countries require that anthrax outbreaks be reported to the appropriate government agencies. Veterinary officials can then supervise the medical treatment of animals, monitor the burning or burial of corpses, and take steps to prevent the spread of the disease. In poor nations, though, shepherds and farmers may not report anthrax outbreaks for several reasons: The animal owners may know little about anthrax and may not even recognize the disease in their livestock; poor farmers and shepherds consider disposing of a carcass to be a waste of meat and hides; burying the remains of anthrax victims entails extra work; and burning a carcass requires wood, which may be scarce or valuable. Thus, in poor regions animal anthrax victims are often skinned and eaten.
Livestock owners in developing nations may also resist vaccinating their herds, even if cost-free vaccine is provided by government agencies. This reluctance is caused by a variety of factors: Farmers are told to rest their animals for two weeks after vaccination, and they may not be willing to stop work for that long. Some livestock owners also believe the vaccine does not work, or fear it will actually spread the disease, because some animals—already infected with anthrax—may die in the weeks following vaccination.
To alleviate these problems, the World Health Organization (WHO) proposes that international agencies educate livestock owners in developing regions about anthrax infection and the dangers of handling, eating, or selling parts (hides, bones, meat, horns) of animals that have died from anthrax. WHO also suggests that poor animal owners be paid for correctly reporting anthrax outbreaks and for disposing of carcasses in an appropriate manner.
Development of Human Anthrax Vaccines
In 1879 John Henry Bell, a physician in Bradford, England, identified woolsorters' disease—a scourge of the wool industry—as human anthrax. Twenty-five years later Frederick Eurich, a scientist at the Bradford and District Anthrax Investigation Board, developed a method of killing anthrax spores by immersing wool and goat hair in formaldehyde, a potent disinfectant. This led to construction of the Government Wool Disinfecting Station in England in 1921, a major step toward controlling woolsorters' disease. After Eurich's death in 1945, a tribute in his hometown newspaper noted: "[Dr. Eurich was] honored wherever wool has to be handled.… Because of the risks he took [working with deadly spores] thousands of wool workers are alive today."16
Animal anthrax vaccines, not approved for people, could not be used to protect wool workers in the first half of the twentieth century. By the time Eurich died, however, human anthrax vaccines were becoming available. The former Soviet Union developed the first human anthrax vaccine, a live-spore vaccine similar to the Sterne animal vaccine, in the 1940s. Great Britain and the United States followed soon afterward, formulating human anthrax vaccines in the 1950s.
The U.S. human anthrax vaccine used today, licensed by the Food and Drug Administration (FDA) in 1970, is produced by Bio-Port Corporation in Lansing, Michigan. The vaccine, called MDPHAVA (Michigan Department of Public Health–Anthrax Vaccine Adsorbed), is made from an unencapsulated (capsule-free) strain of Bacillus anthracis called V770-NP1-R, which has lost some of its ability to cause infection. The vaccine is a cell-free filtrate, containing no whole organisms. Instead, MDPH-AVA is composed of parts of Bacillus anthracis bacteria adsorbed (attached) to particles of aluminum hydroxide. Immunization with MDPH-AVA requires six injections: three injections given two weeks apart followed by three additional injections at six, twelve, and eighteen months. After that, yearly booster shots are needed to maintain immunity.
On the basis of a study conducted in the late 1950s, in which millworkers in four factories in New England were vaccinated, the MDPH-AVA was reported to be almost 93 percent effective. However, anthrax expert Meryl Nass disagrees. Referring to the 1950s study, she observes: "Although the study calculated vaccine effectiveness as 92.5%, I believe that all that can be said is that there is some efficacy, but the actual percent efficacy cannot be calculated due to the small number of cases [in the trial study]."17
The human anthrax vaccine employed in Great Britain is similar to the U.S. vaccine and about as effective. The British vaccine—a cell-free filtrate made from an unencapsulated variety of Bacillus anthracis called strain 34F2—is adsorbed to alum (a double sulfate of aluminum and potassium). In contrast, the human anthrax vaccines used in China and Russia are live-spore vaccines containing attenuated Bacillus anthracis bacteria. These vaccines—which can be injected, scratched into the skin, or administered as a spray—are thought to be very effective. In fact, according to Meryl Nass: "The efficacy of the live Russian vaccine is reported to be greater than that of the killed United States or British vaccines."18 However, the live-spore vaccines can cause severe side effects in people, such as permanent injury to the nervous system, and are considered unsuitable for human use by many nations.
Use of Human Anthrax Vaccines
The U.S. Advisory Committee on Immunization Practices recommends anthrax vaccinations for people who may come into contact with anthrax spores, including scientists and lab workers who study Bacillus anthracis bacteria, employees in industries that use imported animal products, veterinarians working in anthrax-infected areas, and military personnel.
Mass vaccination of the U.S. military began in 1991 during the first Persian Gulf war with Iraq. Because government officials feared Iraq might use biological weapons containing anthrax, soldiers sent to the Persian Gulf received anthrax vaccinations. Six years later, in 1997, the U.S. Department of Defense (DoD) decreed that all active military personnel must be vaccinated against anthrax. The mass vaccination program began in 1998. Thus, since the early 1990s millions of American soldiers have been inoculated with MDPH-AVA.
U.S. health administrators have not recommended anthrax inoculations for the general public for several reasons: The danger of exposure to anthrax is considered remote; the vaccination procedure for MDPH-AVA is complex (six injections plus booster shots); the program would be expensive; and many people might resist being vaccinated. Even for at-risk groups, government officials recommend vaccinating only healthy individuals from eighteen to sixty-five years of age, because anthrax vaccine studies have been restricted to that population. In addition, authorities advise against inoculating pregnant women and children, since vaccine safety has not been established for these groups.
Some experts who doubt the effectiveness and safety of MDPHAVA have reservations about its widespread use for humans. For example, Meryl Nass observes:
There is essentially no good data [about MDPH-AVA]. The one study of this vaccine … only performed active surveillance for forty-eight hours [after inoculation] and one nurse was discouraged from reporting [unfavorable] reactions at the site that administered the most vaccine. We do know … that one vaccinated worker took his mask off in an anthrax "hot room" at Fort Detrick, got a whiff of anthrax and died.19
Peter C.B. Turnbull, another authority on anthrax, also questions the performance and safety of the vaccine. He notes:
Tests in animals have indicated that the protective efficacies of both the United Kingdom and United States vaccines are less than ideal. In addition … the injection into human beings of crude and undefined preparations is increasingly regarded as unsatisfactory, particularly, as in the case of the anthrax vaccines, when they are associated with frequent complaints of unpleasant side-reactions.20
Adverse Reactions to Human Anthrax Vaccine
Information about adverse, or unfavorable, reactions to human vaccination in the United States is reported to the Vaccine Adverse Event Reporting System (VAERS), a joint program of the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). Since 1990 VAERS has received over 120,000 reports from a variety of sources, including vaccine manufacturers, health care providers, state immunization programs, and vaccine recipients.
According to VAERS's records, the most common side effect of inoculation with MDPH-AVA, seen in about 30 percent of recipients, is slight tenderness and redness at the injection site. A more serious reaction, observed in about 5 percent of vaccinated people, is temporary swelling or hardening of the skin around the injection site. A small number of recipients experienced additional side effects, such as headache, itching, fever, chills, nausea, joint pain, body aches, or fatigue.
VAERS's files and physicians' records indicate that about 5 percent of inoculated people experience severe reactions to MDPHAVA, resulting in hospitalization or permanent disability. Dangerous complications include pneumonia, seizures, inflammation of the spinal cord, heart disease, blood poisoning, infection of tissues beneath the skin, inflammation of blood vessels, loss of red blood cells, severe allergic reactions, connective tissue disease, immune system disorders, and Guillain-Barré syndrome (inflammation of the nerves, resulting in temporary loss of feeling and movement). Anthrax inoculations can also cause endocrine glands to fail (the thyroid gland, testes, and adrenal glands stop producing hormones) and Stevens Johnson syndrome (severe skin rashes in which all the skin peels off). Moreover, in a 2002 letter to Emergency Medical News, anthrax expert Meryl Nass writes that "Some … research … suggested that four autoimmune diseases and two cancers were statistically related to anthrax vaccination.… These conditions are multiple sclerosis, diabetes, asthma, Crohn's Disease [an inflammatory disease of the gastrointestinal tract], thyroid cancer and breast cancer." Nass also observes that "Currently, a number of lawsuits are in the courts related to problems with the anthrax vaccine; several involve deaths following anthrax vaccinations."21
Furthermore, the number of adverse reactions to anthrax vaccine may be higher than that reported to VAERS. A 2002 report from the U.S. General Accounting Office (GAO), which monitored anthrax vaccinations among reserve members of the air force and national guard, notes that "the overall rate reported for adverse reactions was nearly three times that published in the vaccine manufacturer's product insert, which claimed only thirty percent would experience some adverse reaction." The GAO report also observes that "among those who took one or more shots … eighty-five percent reported experiencing some type of reaction … [and] of those experiencing side effects, twenty-four percent had adverse effects considered serious enough for the shots to be discontinued."22
Additionally, little research has been done on the long-term effects of MDPH-AVA. One published study, which monitored laboratory workers in Fort Detrick, Maryland, for twenty-five years following vaccination, concluded that they did not develop any serious ailments such as cancer or infertility from the anthrax vaccine. Because of the small number of published accounts, though, the Institute of Medicine of the National Academy of Sciences reported that it could not determine whether anthrax vaccination results in long-term health problems. To find out whether serious illnesses such as cancer are really related to anthrax vaccinations, the DoD is now doing extended studies of MDPH-AVA recipients.
Besides the concerns about side effects and serious illnesses discussed above, there is some concern that anthrax vaccination may be linked to "Gulf War syndrome," an illness experienced by some veterans of the 1991 Persian Gulf War.
Anthrax Vaccine and Gulf War Syndrome
Of the nearly seven hundred thousand U.S. troops that participated in the Persian Gulf War in 1991, over one hundred thousand became ill after returning home. The ailing soldiers reported a variety of symptoms such as headaches, skin rashes, diarrhea, fatigue, confusion, fever, night sweats, joint and muscle pains, dizziness, loss of memory, sleep disturbances, abdominal bloating, lingering bronchitis, vision problems, irritability, and depression. These symptoms are not consistent with any specific disease and were collectively named Gulf War syndrome or Gulf War illness.
The cause of Gulf War syndrome has not been determined. Health officials have suggested a number of possible causes, including side effects of medications or vaccines given to soldiers, exposure to chemical weapons, exposure to biological weapons, exposure to radiation, combat stress, or some combination of these factors.
Many government health officials do not believe the illnesses were caused by the MDPH-AVA. However, the Rockefeller Report of the Senate Committee on Veterans Affairs, issued in 1994, notes:
Although anthrax vaccine had been considered approved prior to the Persian Gulf War, it was rarely used. Therefore, its safety, particularly when given to thousands of soldiers in conjunction with other vaccines, is not well established. Anthrax vaccine should continue to be considered as a potential cause for undiagnosed illnesses in Persian Gulf military personnel because many of the support troops [noncombat troops] received anthrax vaccine, and because the Department of Defense believes that the incidence of undiagnosed illness in support troops may be higher than in combat troops.23
Experts also note that, during a conflict, soldiers are likely to receive anthrax vaccine in combination with other medications. This might have unfavorable health effects. Meryl Nass observes:
Since anthrax vaccine in the future is likely to be used in concert with other [preventive] measures against threat agents like Clostridium botulinum [bacteria that cause botulism] … safety should be demonstrated both when the vaccine is used alone, and also when it is used with other measures, including use with other vaccines and chemical protective agents, such as pyridostigmine and atropine [both used to counteract the effects of nerve gas] and so on.24
Though vaccination with MDPH-AVA may prevent anthrax, many people—especially civilians—have not been inoculated against the disease. If these people are exposed to anthrax, swift medical treatment may prevent serious illness or death.
Treatment for Human Anthrax
If people contract anthrax, antibiotics are used to treat them. Approved antibiotics for anthrax include ciprofloxacin, penicillin, tetracycline, doxycycline, and a number of others. To work well, the antibiotics must be administered during the disease's incubation period or within one day of the appearance of symptoms, before the bacteria begin producing deadly toxins.
Health officials also recommend that antibiotics be administered to people who have been exposed to anthrax spores but show no signs of illness. For example, physicians recommend that people who have had contact with spores, especially airborne spores that cause inhalation anthrax, be treated with "preventive" antibiotics for up to sixty days. Such at-risk individuals may also receive anthrax vaccine as a protective measure.
On occasion, antibiotics administered to anthrax victims cause side effects. Adverse reactions to ciprofloxacin, for example, include diarrhea, nausea, vomiting, skin rashes, headache, stomach pain, mental confusion, tremors, seizures, hallucinations, torn ten-dons, and allergic reactions. Doxycycline is thought to induce fewer side effects but may cause nausea, vomiting, headache, chest pain, facial swelling, throat and tongue inflammation, itching, and hives. Development of additional antibiotics and other means of combating anthrax has become especially important in recent years because of the growing threat that rogue countries and terrorist groups will use anthrax as a biological weapon.