Yes, since 1978, seven independent civilian panels affirmed the safety and efficacy of anthrax vaccine. These include (each discussed in detail below):
The IOM committee reached two major conclusions: that anthrax vaccine works and that anthrax vaccine is as safe as other vaccines. Regarding effectiveness:
"The committee finds that the available evidence from studies with humans and animals, coupled with reasonable assumptions of analogy, shows that AVA as licensed is an effective vaccine for the protection of humans against anthrax, including inhalational anthrax, caused by all known or plausible engineered strains of B. anthracis." [Pages 7 and 58].
The whole report is available at the website of the National Academy Press: Joellenbeck LM, Zwanziger L, Durch JS, Strom BL, editors. The Anthrax Vaccine: Is it Safe? Does it Work? Washington, DC: National Academy Press, March 2002, 235 pages. http://www.nap.edu/catalog/10310.html
When responsibility for vaccine regulation shifted from the National Institutes of Health (NIH) to the Food & Drug Administration (FDA) in 1972, FDA convened a series of civilian advisory panels.
The FDA commissioned these panels to determine whether sufficient evidence of safety and effectiveness existed for vaccine licenses to be continued. These panels considered every vaccine used in America at that time, including such "old" vaccines as polio vaccine, tetanus toxoid, measles vaccine, and many others. The Panel on Review of Bacterial Vaccines & Toxoids met first in 1978 and published their report in 1985 in the Federal Register (1985; 50:51002-117).
The panel consisted of prominent infectious disease experts and other physicians and scientists with expertise in pharmaceutical manufacturing quality. The panel recommended that the federal licenses for each bacterial vaccine be continued, but the panel recommended that several other product licenses be terminated. In the case of anthrax vaccine, this civilian panel concluded: "The Panel recommends that this product be placed in Category I and that the appropriate license(s) be continued because there is substantial evidence of safety and effectiveness for this product." The FDA accepted this recommendation completely. FDA revoked the licenses for the other products, following the recommendations of the civilian panel.
The Advisory Committee on Immunization Practices (ACIP) consists of America's preeminent vaccine scientists, civilian physicians who advise the Centers for Disease Control & Prevention (CDC) (http://www.cdc.gov/nip/publications/ACIP-list.htm). The ACIP sets national standards for vaccine delivery. ACIP guidelines for the nation are published in the CDC's weekly journal, the Morbidity & Mortality Weekly Report (MMWR).
Between fall 1999 and June 2000, an ACIP working group reviewed published and unpublished information about anthrax vaccine adsorbed (AVA). In June 2000, the ACIP unanimously adopted a report finding anthrax vaccine effective and safe for the prevention of anthrax. The report notes that: "The efficacy of AVA is based on several studies in animals, one controlled vaccine trial in humans, and immunogenic data for both humans and lower mammalian species. ...Routine vaccination with AVA is indicated for persons engaged in work involving production quantities or concentrations of B. anthracis cultures and in activities with a high potential for aerosol production."
The ACIP recognizes that it is the role of the Defense Health Board (DHB) to advise the military Surgeons General on vaccination policies for military personnel. Nonetheless, the ACIP noted that "For the military and other select populations or for groups for which a calculable risk can be assessed, pre-exposure vaccination may be indicated." Advisory Committee on Immunization Practices. Use of anthrax vaccine in the United States MMWR-Morbidity & Mortality Weekly Report 2000; 49(RR-15):1-20. http://www.cdc.gov/mmwr/PDF/rr/rr4915.pdf
The Working Group on Civilian Bio-defense included 23 representatives from staff of major academic medical centers and research, government, military, public health, and emergency management institutions and agencies. The original consensus statement of 1999 resulted from a synthesis of published information and the revision of three drafts. Members of the working group reviewed anthrax literature again in January 2002, with special attention to articles following the anthrax attacks of 2001. Members commented on a revised document with proposed revisions being incorporated in the final product put out by The Center for Civilian Bio-defense Strategies (http://www.hopkins-biodefense.org/). The working group concurred with the findings of the March 2002 IOM report on the safety and efficacy of AVA, that AVA is effective against inhalational anthrax and concluded that if given with appropriate antibiotic therapy, it may help prevent the development of disease after exposure. The working group also found that: "Pre-exposure vaccination of some persons deemed to be in high-risk groups should be considered when substantial supplies of vaccine become available."
The working group also addressed the use of anthrax vaccine in children: "The U.S. anthrax vaccine is licensed for use only in persons aged 18 to 65 years because studies to date have been conducted exclusively in this group. No data exist for children, but based on experience with other inactivated vaccines, it is likely that the vaccine would be safe and effective." Inglesby TV, O'Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, Gerberding J, Hauer J, Hughes J, McDade J, Osterholm MT, , Parker G, Perl TM, Russell PK, Tonat K, Working Group on Civilian Bio-defense. Anthrax as a biological weapon, 2002: Updated recommendations for management. Journal of the American Medical Association 2002; 287:2236- 52. http://jama.ama-assn.org/cgi/content/short/287/17/2236
The Defense Health Board (DHB), formerly known as Armed Forces Epidemiological Board (AFEB), has a proud 60-year heritage of protecting the health of America's Armed Forces. The DHB consists of civilian physicians and scientists selected to advise the Surgeons General of the Armed Services (http://www.ha.osd.mil/DHB/default.cfm).
From its first reviews of anthrax vaccine under DoD Directive 6205.3, the DHB has affirmed the value of this vaccine. In August 1994, the DHB concluded: "The licensed anthrax vaccine is suitable for use in personnel assigned, pre-designated or scheduled for deployment to areas with a validated higher threat under its approved indications." In November 1996, the Defense Health Board reported that it "endorses the proposed DoD anthrax vaccine implementation plan under the current vaccine protocol [i.e., dosing schedule]."
The DHB reaffirmed its recommendations to use anthrax vaccine for bio-defense of military personnel in 1999 and 2000. A March 25, 1999, report states "The DHB continues to strongly endorse the current DoD Anthrax Vaccine Immunization Program."
On March 29, 2000, the DHB reported: "...we are (DHB) concerned and somewhat surprised at the criticism surrounding the program given the high level of professionalism that had characterized this effort... Anthrax vaccine is a fully licensed FDA vaccine.
The vaccine does cause local side effects, but has an excellent safety profile. The Anthrax Vaccine Immunization Program has carefully tabulated person-specific immunization data and has assiduously investigated reported complications associated with receipt of anthrax vaccine. These data have been regularly reviewed by the board and attest to the safety of the vaccine." http://www.anthrax.mil/resource/library/afeb.asp
The DHB continues to receive regular updates regarding implementation of the Anthrax Vaccine Immunization Program and the variety of safety surveillance methods used by the Department of Defense to monitor the vaccine's use.
The vaccine schedule should be followed as closely as possible. However, if a person is late for a dose, the next dose should simply be given as soon as possible. Then subsequent doses should be given according to the standard dosing intervals from the most recent dose. This applies to anthrax vaccine, as well as other vaccines, according to the Centers for Disease Control & Prevention. http://www.cdc.gov/mmwr/PDF/rr/rr4915.pdf
If an annual booster has not been administered on time, administer the booster dose at the earliest possible date, adjusting the subsequent booster schedule accordingly. Once the primary series of five doses is complete, the primary series is never repeated.
The current FDA-licensed schedule calls for doses to be administered intramuscularly in the deltoid according to the following schedule (the first dose is considered "week 0"): 0, 4 weeks; 6 months, 12 months, and 18 months.
Recipients receive the first shot, then the second shot four weeks later, and then the third shot five months after the second shot. Six months after the third shot, recipients receive the fourth shot. Six months after that, they receive the fifth shot. The entire primary series takes 18 months to complete. Annual booster doses of the vaccine are required for ongoing protection.
On 11 Dec 08, the Food and Drug Administration (FDA) approved two updates to the package insert for the anthrax vaccine. The route of administration was changed from a subcutaneous injection over the deltoid to an intramuscular injection in the deltoid. The FDA also approved a change in the vaccination series by removing the 2-week dose. The new schedule is now 0, 4 weeks, and 6 months, 12 months, 18 months, and annual boosters.
Brachman PS, Friedlander AM, Grabenstein JD. Anthrax. In: Plotkin SA, Orenstein WA, Vaccines, 4th ed. Philadelphia: W. B. Saunders, 2003.
Brachman PS, Gold H, Plotkin SA, Fekety FR, Werrin M, Ingraham NR. Field evaluation of a human anthrax vaccine. American Journal of Public Health 1962;52:432-45. http://www.anthrax.mil/documents/338field_eval.pdf
Advisory Committee on Immunization Practices. Use of anthrax vaccine in the United States. MMWR-Morbidity & Mortality Weekly Report 2000;49(RR-15):1-20. http://www.cdc.gov/mmwr/PDF/rr/rr4915.pdf
Food & Drug Administration. Biological products; Bacterial vaccines and toxoids; Implementation of efficacy review. Federal Register 1985;50:51002-117. http://www.anthrax.mil/documents/338field_eval.pdf
Franz DR, Jahrling PB, Friedlander AM, McClain DJ, Hoover DL, Bryne WR, Pavlin JA, Christopher GW, Eitzen EM Jr. Clinical recognition and management of patients exposed to biological warfare agents. Journal of the American Medical Association 1997;278(Aug 6):399-411. http://jama.ama-assn.org/cgi/content/short/278/5/399
Hambleton P, Carman JA, Melling J. Anthrax: The disease in relation to vaccines. Vaccine 1984;2:125-32.
Inglesby TV, O'Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, Gerberding J, Hauer J, Hughes J, McDade J, Osterholm MT, , Parker G, Perl TM, Russell PK, Tonat K, Working Group on Civilian Biodefense. Anthrax as a biological weapon, 2002: Updated Recommendations for Management. Journal of the American Medical Association 2002;287:2236- 52. http://jama.ama-assn.org/cgi/content/short/287/17/2236
Ivins BE, Fellows PF, Pitt MLM, Estep JE, Welkos SL, Worsham PL, Friedlander AM. Efficacy of a standard human anthrax vaccine against Bacillus anthracis aerosol spore challenge in rhesus monkeys. Salisbury Medical Bulletin 1996;87(Suppl): 125-6.
Ivins BE, Pitt MLM, Fellows PF, Farchaus JW, Benner GE, Waag DM, Little SF, Anderson GW Jr., Gibbs PH, Friedlander AM. Comparative efficacy of experimental anthrax vaccine candidates against inhalation anthrax in rhesus macaques. Vaccine 1998;16:1141-8.
Pitt MLM, Ivins BE, Estep JE, et al. Comparison of the efficacy of purified protective antigen and MDPH to protect non-human primates from inhalation anthrax. Salisbury Medical Bulletin. 1996;87:130.
Sidell FR, Takafuji ET, Franz DR. Medical Aspects of Chemical & Biological Warfare. Washington, DC: Department of the Army, 1997.
Turnbull PCB. Guidelines for the Surveillance and Control of Anthrax in Humans and Animals, 3rd ed., WHO Report WHO/EMC/ZDI/98.6.
Food & Drug Administration. Biological products; Bacterial vaccines and toxoids; Implementation of efficacy review. Federal Register 1985;50:51002-117. http://www.anthrax.mil/documents/205Fed_Reg.pdf
Food & Drug Administration. Biological products; Bacterial vaccines and toxoids; Implementation of efficacy review. Federal Register 2004;29:78281-93. http://www.anthrax.mil/documents/library/bvactox.pdf
In nearly 30 years of licensed use, there is no evidence of any sterility or fertility impairment from anthrax vaccine. Regarding reproductive health, the Center for Disease Control and Prevention's Advisory Committee on Immunization Practices states, "there is no convincing risk from vaccinating pregnant women with inactivated virus or bacterial toxoids."
In the March 27, 2002, issue of the Journal of American Medical Association, two Army physicians published their peer-reviewed findings that women get pregnant at the same rate, whether anthrax-vaccinated or unvaccinated. These physicians from Fort Stewart, Georgia, also showed that women deliver offspring at the same rate, whether anthrax-vaccinated or unvaccinated. The Fort Stewart study found no difference in birth defect rates, but the study may have been too small to detect small differences. [Wiesen AR, Littell CT. Relationship between pre-pregnancy anthrax vaccination and pregnancy and birth outcomes among U.S. Army women. Journal of the American Medical Association (JAMA) 2002; 287:1556-60. http://jama.ama-assn.org/content/vol287/issue12/index.dtl.
Preliminary data from the Naval Health Research Center raised a tentative signal that there may be an association with an increased rate of birth defects if vaccinated in the first trimester of pregnancy. This signal is being investigated thoroughly, to determine which of several explanations for the signal is most likely.
Long-standing Defense policy is to defer routine vaccinations in women until after pregnancy. This policy has always applied to anthrax vaccine. Women are asked if they are pregnant before vaccination. Women who are not sure are offered pregnancy tests.
Data about anthrax vaccination was obtained from men at time of oocyte and sperm retrieval. Researchers assessed characteristics of male gametes, including 254 vaccinated men and 791 unvaccinated men. The two groups were comparable for semen concentration (million sperm per milliliter), sperm motility (movement), sperm morphology (shape), need for intracytoplasmic sperm injection, and rate of fertilization of mature oocytes, embryo transfer, and clinical pregnancy. A diagnosis of male-factor infertility was less common in anthrax-vaccinated men than in unvaccinated men. The researchers concluded that anthrax vaccination of men did not impair semen parameters, fertilization rate, embryo quality, or clinical pregnancy rates.
In addition to the Department of Defense, other agencies and groups advocate or support the use of the anthrax vaccine. The Food & Drug Administration licensed the anthrax vaccine in 1970. The Centers for Disease Control & Prevention, the World Health Organization, the Defense Health Board, and many other respected public health organizations support use for people at risk or exposed to Bacillus anthracis. Information about the AVIP is available on the Internet (a variety of DoD web sites as well as the Centers for Disease Control & Prevention (www.cdc.gov) and the Food & Drug Administration web sites), which includes facts about the anthrax vaccine, history, side effects, purpose for immunizations and more. [See the Q&A page on independent scientific reviews.] Evidence for the efficacy of the anthrax vaccine is sufficient for it to be included in standard medical reference books in the United States and around the world. These references include:
Advisory Committee on Immunization Practices. General recommendations on immunization. MMWR-Morbidity & Mortality Weekly Report 2002;51(RR-2):1-35. ftp://ftp.cdc.gov/pub/Publications/mmwr/rr/rr5102.pdf
American College of Obstetricians & Gynecologists, Committee Opinion, Immunization During Pregnancy, 2003;282:1-6. http://www.acog.org/from_home/publications/misc/bco282.pdf
Brachman PS, Friedlander AM, Grabenstein JD. Anthrax. In: Plotkin SA, Orenstein WA, ed. Vaccines, 3rd ed. Philadelphia: W. B. Saunders, 2003.
Catherino WH, Levi A, Leondires M, Segars JH, Alvero R, McKeeby J. Fertility & Sterility Abstracts Vol. 78, No. 3, Suppl. 1, September 2002, pages S108-S109. http://www.vaccines.mil/documents/library/Fertility&Sterility.pdf
Christopher GW, Cieslak TJ, Pavlin JA, Eitzen EM Jr. Biological warfare: A historical perspective. Journal of the American Medical Association 1997;278(Aug 6):412-17. http://jama.amaassn.org/cgi/content/short/278/5/412
Inglesby TV, O'Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Friedlander AM, Gerberding J, Hauer J, Hughes J, McDade J, Osterholm MT, , Parker G, Perl TM, Russell PK, Tonat K, Working Group on Civilian Biodefense. Anthrax as a biological weapon, 2002: Updated Recommendations for Management. Journal of the American Medical Association 2002;287:2236- 52. http://jama.ama-assn.org/cgi/reprint/287/17/2236.pdf
Peeler RN, Cluff LE, Trever RW. Hyper-immunization of man. Bulletin of the Johns Hopkins Hospital 1958;103:183-98. Peeler RN, Kadull PJ, Cluff LE. Intensive immunization of man: Evaluation of possible adverse consequences. Annals of Internal Medicine 1965;63:44-57.
Singleton JA, Lloyd JC, Mootrey GT, Salive ME, Chen RT, VAERS Working Group. An overview of the vaccine adverse event reported system (VAERS) as a surveillance system. Vaccine 1999;17:2908-17. Turnbull PCB. Guidelines for the Surveillance and Control of Anthrax in Humans and Animals, 3rd ed., WHO Report WHO/EMC/ZDI/98.6. http://www.who.int/emcdocuments/zoonoses/whoemczdi986c.html
White CS III, Adler WH, McGann VG. Repeated immunization: Possible adverse effects: Reevaluation of human subjects at 25 years. Annals of Internal Medicine 1974;81:594 600. http://www.vaccines.mil/documents/library/Repeated.pdf
At Fort Detrick, Maryland, 99 laboratory workers were evaluated 10 to 20 years after receiving anthrax vaccine. Most of these workers received 150 to 200 doses of various vaccines (including anthrax vaccine); some received more than 300 such injections during their tenure at Fort Detrick. This study "failed to produce evidence that development of neoplasms, amyloidosis, or autoimmune diseases was associated with the vaccine dosages and frequencies used at Fort Detrick. The authors concluded "These data and the accompanying evaluation of an intensively immunized population provide evidence that no obvious adverse effects result from repeated immunization." The first report of this group of vaccine recipients was published in the Bulletin of the Johns Hopkins Hospital in 1958. Two follow-up reports were published in the Annals of Internal Medicine in 1965 and 1974.
An extension of this long-term study is underway at the U.S. Army Medical Research Institute for Infectious Diseases (USAMRIID) to determine, in even greater detail, whether people who received multiple vaccines, including anthrax vaccine, during their past employment at Fort Detrick demonstrated any adverse health effects over the long term. More than 1,500 employees have been followed annually there. In a case-control study begun in 1996, vaccinated and unvaccinated volunteers have been enrolled. All volunteers signed an informed-consent document. The study methods include a 9-page health history questionnaire, extensive blood tests and urinalysis. The questionnaire queries mental and physical conditions of the volunteers, as well as the health of their offspring. Study end points include symptoms, symptom complexes (including symptoms reported by veterans of the Persian Gulf War), diseases, and abnormal laboratory and urine tests. Study subjects will be compared to two to three race-, gender-, and age-matched control subjects to determine if any long-term medical effects exist among this unique group of study subjects. Analysis of the data from the extensive health history questionnaire and numerous laboratory tests are currently in progress. No unexplained symptoms due to repeated doses of anthrax or other vaccines have been found. From this and other monitoring, no patterns of delayed side effects to anthrax vaccine have been found. Monitoring continues. White CS III, Adler WH, McGann VG. Repeated immunization: Possible adverse effects: Reevaluation of human subjects at 25 years. Annals of Internal Medicine 1974; 81:594-600.
A recent study by the Department of Defense (DoD) Center for Deployment Health Research with the Naval Health Research Center and the National Center for Birth Defects and developmental Disabilities indicated that women who received anthrax vaccinations during their first trimester of pregnancy could have a slightly higher risk of birth defects than women receiving anthrax vaccine at other times before or after the first trimester. The study is still under review. Results are pending.
The Special Assistant for Gulf War Illnesses, Dr. Bernard Rosker, published an info paper entitled "Vaccine Use During the Gulf War" (http://www.gulflink.osd.mil/va/). When Persian Gulf War veterans returned and started reporting symptoms, some people asked if vaccines administered during the Gulf War might have caused the symptoms. Several independent expert panels addressed this and related questions head-on. These panels consisted of Veterans, civilian academic experts, scientists, health-care professionals, and policy specialists. Each of these panels included some of the nation's best scientists, who spent months or even years listening to veterans, reviewing the evidence, and deliberating the issues.
In each case, the independent expert panels found that there was no evidence of any link between any vaccine and any illness common to Gulf War veterans. These reports include:Presidential Advisory Committee on Gulf War Veterans' Illnesses: Final Report, December 1996. Pages of Interest: second page, Executive Summary, plus pages 112-114 of the original document (Chapter 4 in the web version). Institute of Medicine, Health Consequences of Service During the Persian Gulf War:Recommendations for Research & Information Systems, 1996. (http://books.nap.edu/books/0309055369/html/1.html)Pages of Interest: 49-52, 55, 100. National Institutes of Health, Technology Assessment Workshop: The Persian Gulf Experience and Health, 29 April 1994. Defense Science Board Task Force on Persian Gulf War Health Effects, June 1994. (http://www.gulflink.osd.mil/dsbrpt/index.html) See chapter VIII, section E.2. Three specific studies looking into the health of Gulf War veterans and their families were published in the New England Journal of Medicine. The postwar hospitalization experience of U.S. veterans of the Persian Gulf war. New England Journal of Medicine 1996; 335:1505-13. This study concluded that "During the two years after the Persian Gulf War, there was no excess of unexplained hospitalization among Americans who remained on active duty after serving in that conflict." The risk of birth defects among children of Persian Gulf war veterans. New England Journal of Medicine 1997; 336:1650-6. The authors concluded that "This analysis found no evidence of an increase in the risk of birth defects among the children of Gulf War veterans." Mortality among U.S. veterans of the Persian Gulf war. New England Journal of Medicine 1996; 335:1498-1504. The authors concluded: "Among veterans of the Persian Gulf War, there was a significantly higher mortality [death] rate than among veterans deployed elsewhere, but most of the increase was due to accidents rather than disease, a finding consistent with patterns of postwar mortality among veterans of previous wars." A DoD-funded British team at King's College, London, reported in the 20 May 00 issue of British Medical Journal that multiple vaccinations given in a theater of war, but not before deployment, were associated with multi-symptom illness, fatigue, psychological distress, health perception, and physical functioning. The analysis was limited to veterans who kept vaccination records.
Exposures other than vaccination were not controlled for, except pesticide use. Anthrax vaccine was not analyzed independently. The lead author was Matthew Hotopf; the research team included Catherine Unwin. The authors recommend that Armed Forces be vaccinated before deployment: "It would be folly to allow Service personnel to be committed to a modern battlefield without all necessary means of protection against endemic infection and biological weapons." The accompanying editorial calls Hotopf's evidence "inconclusive," citing design limitations and contradictory findings.