Entry last updated: May 27, 2004
- Understanding the Disease
- Available Vaccines
- History of the Vaccine
- Who Should and Should Not Receive the Vaccine
- Dose Schedule
- Effectiveness of the Vaccine
- Known Side Effects
- Related Issues
- Key References and Sources of Additional Information
Understanding the Disease
Anthrax is a deadly infectious disease caused by spore-forming bacteria called Bacillus anthracis. Anthrax is primarily a disease of livestock, but can infect humans when they are exposed to infected animals or contaminated products, such as animal hides, hair or wool, or contaminated soil near these animals.
The disease is uncommon in the United States. Before the recent cases of anthrax, less than 250 cases had been reported in the United States since 1955. In contrast, the disease is still common in parts of South and Central America, Southern and Eastern Europe, Asia, Africa, the Caribbean, and the Middle East, where control of anthrax by vaccination of livestock is inadequate. In these settings, exposure to anthrax spores dormant in the soil is the most likely source of infection.
Anthrax has long been recognized as a potential biological weapon, particularly if spores are released into the air. Many scenarios have demonstrated the potential for substantial morbidity, mortality and social disruption after an aerosol release of anthrax over an urban area.
Recent events, such as those related to contact with anthrax spores in envelopes in the postal system, further highlight the impact of anthrax as a biological weapon.
The three main routes of anthrax infection are through broken skin (cutaneous anthrax), by eating contaminated food (gastrointestinal anthrax), and by breathing anthrax spores (inhalation anthrax). Of anthrax cases reported in the United States, 95% are cutaneous. The fatality rate for cutaneous anthrax is 5% to 20% without antibiotic treatment and <1% with antibiotics. For those exposed through the digestive tract, the case fatality is estimated to be 25% to 60%.
Before the availability of antibiotics or a vaccine, inhalation anthrax was almost always fatal. However, more recent experience suggests that early diagnosis and treatment improves the prognosis and outcome. Although the illness may start like many respiratory illnesses�with muscle aches and pains, fever, fatigue, cough, mild chest discomfort, and just not feeling well (general malaise)�these symptoms are followed in a few days by an abrupt onset of difficulty breathing and a rapid heart rate.
Recent patients with anthrax reported symptoms of headache and abdominal discomfort. Within 24 to 36 hours, the patient cannot breathe in enough oxygen, develops shock, and is in critical condition, often leading to death. In the absence of antibiotic treatment, patients with cutaneous and gastrointestinal anthrax may develop bacteremia (infection of the blood) and meningitis (inflammation of the brain and spinal cord coverings). The development of these complications is often a sign of an overwhelming infection that may be difficult to cure.
Product: BioThrax� (anthrax vaccine adsorbed; AVA)
Manufacturer: BioPort Corporation
Licensure Date: 1970
The anthrax vaccine has been licensed in the U.S. since 1970. It is manufactured by BioPort Corporation, formerly Michigan Biologic Products Institute.� Although there were delays in�FDA approval of Bioport's renovated manufacturing plant, the FDA licensed Bioport to begin routine distribution of the vaccine from its facility as of January 31, 2002.
A new recombinant vaccine, which�should have much fewer reactions, is under development by the National Institutes of Health.
For information on the thimerosal content in this vaccine, see the Food and Drug Administration at www.fda.gov/cber/vaccine/thimerosal.htm#t3
or Johns Hopkins University's Institute for Vaccine Safety at
History of the Vaccine
The modern form of anthrax vaccine was first developed in the United States in the 1940s and 1950s. This vaccine was found to be safe and effective in preventing anthrax infection in mill workers in the late 1950s. A purer, more potent form of the anthrax vaccine was later developed, which the Food and Drug Administration (FDA) licensed in November 1970.
Between 1974 and 1989, 68,000 doses of anthrax vaccine were distributed in the United States. Additionally, during the Persian Gulf War of 1990-1991, an estimated 150,000 military personnel received 268,000 doses of anthrax vaccine. Since March 1998, more than 524,000 military personnel received more than 2.1 million doses of anthrax vaccine.
Recent Bioterrorism-Related Events: Until recently, the vaccine was offered to military personnel and to laboratory workers at special risk for anthrax infection. On December 17, 2001, the Department of Health and Human Services (HHS) announced that it would offer the vaccine to postal workers and Capitol Hill employees who were exposed to inhalation anthrax in the recent mail attacks. The HHS announcement came after a December 15 meeting at the National Academy of Sciences, during which scientists discussed whether the vaccine would benefit people exposed to anthrax spores. The full transcript of this meeting, Optimizing Post-Exposure Prevention of Inhalation Anthrax: Issues and Options, can be found here.
The current vaccine was licensed by the FDA on the basis of its ability to prevent an anthrax infection among people prior to potential exposure. Because of concerns about the quantity of the anthrax spores involved in the recent events, and animal experiments that demonstrate that spores can persist in the lungs for months before germinating and causing a serious infection, the vaccine is now being made available to people who have already been exposed. The goal is to provide additional protection to people already exposed in order to minimize their chances of developing an infection over the coming months.
However, because the vaccine has not previously been used in this way, it is important that people who are considering immunization in this setting need to understand that immunization after exposure is a form of clinical research. Because this is considered an investigational use of an approved vaccine drug, informed consent is required, and scientists will follow up to evaluate whether post-exposure immunization is effective at preventing infection in people already exposed. People immunized in this way should be fully informed about the nature and expected outcomes of this study. In addition, before entering such a study, potential volunteers should be aware of the known side effects as well as the potential benefit of the vaccine used in this way. An explanation of this study can be viewed at: www.hhs.gov/news/press/2001pres/20011218.html
Who Should and Should Not Receive this Vaccine
Who should receive this vaccine?
Who should not receive this vaccine for post-exposure protection?
- People who have recovered from an anthrax infection (they may be immune to further infection)
- People who developed a serious allergic (anaphylactic) reaction to a previous dose of anthrax vaccine (the vaccine could be dangerous to them)
Who should not receive this vaccine for pre-exposure protection?
When given to prevent anthrax infection before exposure, the standard schedule consists of six doses administered just under the skin (subcutaneously). Following the first dose, additional doses of vaccine are given at�two and�four weeks, followed by booster doses 6, 12, and 18 months later. Finally, an annual booster dose is recommended to maintain prolonged immunity.
In the study to prevent anthrax infection among postal workers and Capitol Hill employees who may have already been exposed, recipients of the vaccine will receive a three-dose course with doses separated by two weeks.
Effectiveness of the Vaccine
In 1962, a controlled study with mill workers found that the anthrax vaccine was 92.5% effective at protecting against anthrax. The 92.5% statistic included both cutaneous and inhalational cases of anthrax. Looking at inhalational anthrax alone, five cases occurred among unvaccinated people, while zero cases occurred among vaccinated people, but the number of cases was too small to allow a specific statistical comparison for inhalational disease by itself
Because there have been so few human cases of inhalational anthrax, scientists conducted animal studies to test the anthrax vaccine. In Rhesus monkeys given one or two doses of anthrax vaccine, 95% survived an inhalational challenge with hundreds of times the number of anthrax spores that are considered to be lethal. Every unvaccinated monkey died in these tests. �Animal studies cannot be directly applied to human beings, but are often useful in guiding decisions for humans.
As with most vaccines, measuring anthrax antibody levels provides only an indirect measure of the vaccine�s ability to prevent disease. However, 91% of adults who receive the anthrax vaccine show an immune response after two or more doses, and 95% have a four-fold increase in antibodies after three doses. The higher level of anthrax antibodies are thought to protect the vaccine recipient against anthrax, though scientists do not know the precise level of antibody at which protection against anthrax can be assured.
The anthrax vaccine is the only aluminum-containing vaccine that is given under the skin (subcutaneous administration), rather than directly into the muscle (intramuscular administration). Aluminum is incorporated into many vaccines to increase their potency and produce the desired protection. Because it is felt that giving the vaccine subcutaneously is responsible for the high number of local side effects (temporary soreness, redness, swelling, itching and lumps at the injection site in 30% of male recipients and 60% of female recipients), CDC has initiated a human clinical trial of the anthrax vaccine to compare these two routes of administration. In this study, the volunteers will receive anthrax vaccinations administered either just under the skin or in the muscle, on various dosing schedules. Comparisons will be made of the side effects and the immune responses. The volunteers will not be exposed to anthrax spores or other health risks.
The CDC's Advisory Committee on Immunization Practices (ACIP) also has recommended clinical toxicology studies among pregnant animals to determine safety of the anthrax vaccine during pregnancy. In addition, research is also needed to determine the specific point at which the vaccine makes a person immune.
Known Side Effects
Anthrax vaccine may cause soreness, redness, itching, swelling, and lumps at the injection site. About 30% of men and 60% of women report mild local reactions, usually lasting only a few days. Lumps can persist for a few weeks.� Between 1% and 5% of those who receive the vaccine�report moderate reactions (redness, swelling) of one to five inches in diameter. Larger reactions occur in 1% of vaccine recipients.
Some people will experience rashes (16%), headaches (14% to 25%), and joint aches (12% to 15%), malaise (6% to 17%), muscle aches (3% to 34%), nausea (3% to 9%), chills (2% to 6%) or fever (1% to 5%) after vaccination.� These symptoms usually go away after a few days. Severe allergic reactions have been reported in less than one out of every 100,000 doses administered.
Some have raised concerns about potential long-term effects of anthrax vaccine and questioned the overall safety of the vaccine. A March 2000 report by the Institute of Medicine�s Committee on Health Effects Associated with Exposures during the Gulf War noted that �to date, published studies have reported no significant adverse effects of the vaccine, but the literature is limited to a few short-term studies.�
A�review of surveillance for adverse events following anthrax vaccination found that, although there are short-term side effects�more common among women than men��no patterns of unexpected local or systemic adverse events have been identified.�
Additional studies have been presented to another Institute of Medicine committee. A list of these articles has been compiled by the Anthrax Vaccine Immunization Program (AVIP) Agency.
For more information on anthrax bioterrorism see:
- American Academy of Pediatrics. (2001). Children, bioterrorism, and disasters [Web page].�
- Centers for Disease Control and Prevention (CDC). (2001). Information about anthrax and bioterrorism [Morbidity and Mortality Weekly Report].
- CDC. (2001).�Emergency preparedness and response�[Web site].�
- CDC, Advisory Committee on Immunization Practices. (2000). Use of anthrax vaccine in the United States. Morbidity and Mortality Weekly Report; 49(RR-15), 1-20.
- Jernigan JA, Stephens DS, Ashford DA, Omenaca C, Topiel MS, Galbraith M, Tapper M, Fisk TL, Zaki S, Popovic T, Meyer RF, Quinn CP, Harper SA, Fridkin SK, Sejvar JJ, Shepard CW, McConnell M, Guarner J, Shieh WJ, Malecki JM, Gerberding JL, Hughes JM, and Perkins BA. (2001). Bioterrorism-related inhalational anthrax: The first 10 cases reported in the United States. Emerging Infectious Diseases, 7(6), 933-944.�
- Center for Biosecurity, UPMC. (2001). Case studies of bioterrorism-related inhalational anthrax
For more information on the military anthrax program, see the official U.S. Department of Defense Anthrax Vaccine Immunization Program (AVIP) website.
For more information about the anthrax vaccine, visit Bioport Corporation�s web site�or call 517-327-1500.
The vaccine's safety and efficacy has reviewed a variety of independent civilian panels. These include:
- Centers for Disease Control and Prevention (CDC). (2000). Use of anthrax vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report, 49(RR-15), 1-20.
- Demicheli V, Rivetti D, Deeks JJ, Jefferson T, and Pratt M. (1998). The effectiveness and safety of vaccines against human anthrax: A systematic review. Vaccine, 16(9-10), 880-884.
- Food and Drug Administration. (1985). Biological products: Bacterial vaccines and toxoids: Implementation of efficacy review. Federal Register, 50(240), 51002-51117.��
- Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, Hauer J, McDade J, Osterholm MT, O'Toole T, Parker G, Perl TM, Russell PK, and Tonat K. (1999). Anthrax as a biological weapon: Medical and public health management [Consensus statement from the Working Group on Civilian Biodefense]. JAMA, 281(18), 1735-1745.
- Institute of Medicine, Committee on Health Effects Associated with Exposures During the Gulf War. (2000). An assessment of the safety of the anthrax vaccine: A letter report. Washington, DC: Author.�
Key References and Sources of Additional Information
- American Academy of Pediatrics, Committee on Infectious Diseases. (2003). Anthrax. In Red Book: Report of the Committee on Infectious Diseases (26th ed., pp. 196-199). Elk Grove Village, IL: Author.
- Brachman PS, Gold H, Plotkin SA, Fekety FR, Werrin M, and Ingraham NR. (1962). Field evaluation of a human anthrax vaccine. American Journal of Public Health, 52, 432-445.
- Brachman S and Friedlander AM. (1999). Anthrax. In Plotkin SA and Orenstein WA (Eds.). Vaccines (3rd ed., pp. 629-637). Philadelphia: W. B. Saunders.
- Brachman P and Kauffman A. (1998). Anthrax. In Evans AS and Brachman PS (Eds.). Bacterial infections of humans. New York: Plenum Medical Book Company.
- Centers for Disease Control and Prevention (CDC). (2000). Anthrax vaccine: What you need to know [Vaccine Information Statement (VIS)].
- CDC. (2000). Human ingestion of bacillus anthracis-contaminated meat�Minnesota, August 2000. Morbidity and Mortality Weekly Report, 49 (36), 813-816.
- CDC. (2000). Surveillance for adverse events associated with anthrax vaccination - U.S. Department of Defense, 1998-2000. Morbidity and Mortality Weekly Report, 49 (16), 341-345.
- Chin J (Ed.). (2000). Control of communicable diseases manual (17th ed.). Washington, DC: American Public Health Association.
- Dixon TC, Meselson M, Guillemin J, and Hanna PC. (1999). Anthrax. New England Journal of Medicine, 341(11), 815-826.
- Friedlander AM, Pittman PR, and Parker GW. (1999). Anthrax vaccine: Evidence for safety and efficacy against inhalational anthrax. JAMA, 282(22), 2104-2106.�
- National Institutes of Health, U.S. Department of Health and Human Services� Office of Public Health Preparedness, and the CDC. (2001, December). Optimizing post-exposure prevention of inhalation anthrax: Issues and options. Transcript of meeting held at the National Academy of Sciences, Washington, DC.
- Plotkin SA. (2001). Immunologic correlates of protection induced by vaccination. Pediatric Infectious Disease Journal, 20 (1), 63-75.
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