Anthrax
Display Page Index  + 
Bacillus anthracis
stain of anthrax

Bacillus anthracis is an aerobic, spore-forming bacterium that causes anthrax disease. Anthrax occurs globally, especially in agricultural areas that do not have a livestock vaccination program. Naturally occurring anthrax is rare in the United States, which has successful vaccination programs among livestock and strict importation regulations. In 2001, anthrax bacteria were used in bioterrorism attacks involving the postal system and government buildings. Regardless of the cause, all suspected cases of anthrax must be reported to the local health department for investigation.

Anthrax bacteria infect people and animals when spores are inhaled, ingested, or enter the body through a break in the skin. Once inside the body, the spores replicate and produce three proteins: edema factor (EF), lethal factor (LF), and protective antigen (PA). It is the combination of these proteins that is believed to cause tissue damage, shock, and death. Sometimes there is a delayed onset of anthrax disease. This is because anthrax spores can remain in the lungs for weeks without replicating. Antibiotics do not kill the spores. When the spores finally do replicate, anthrax disease develops.

There are three forms of anthrax disease:

  • Cutaneous (Skin)
    Incubation period: 1-12 days
    Signs and symptoms: painless lesion(s) with black center
  • Gastrointestinal (Ingestion)
    Incubation period: 1-7 days
    Signs and symptoms: throat ulcers, abdominal pain, fever, bloody diarrhea, vomiting
  • Inhalation
    Incubation period: 1-7 days (can be longer)
    Signs and symptoms: initially presents as flu-like symptoms, such as non-productive cough, myalgia, fatigue, and fever. In later stages there may be brief improvement, followed by high fever, dyspnea, cyanosis, and shock.
    This is the most dangerous form of anthrax, with case-fatality rates of up to 75% even with antibiotic therapy. Death can occur within hours of the onset of symptoms.

Antibiotics, such as ciprofloxacin, doxycycline, and amoxicillin, are the most important therapeutic interventions for any form of anthrax. A combination of antibiotics needs to be started as soon as the disease is suspected. In addition, aggressive supportive care will be needed.

About the Vaccine

In 1991, DoD Service members deploying for the Persian Gulf War received one or two doses of anthrax vaccine, labeled Vaccine A or Vacc A. Other abbreviations for anthrax vaccine include AVA and ANT. Before November 2008, the vaccine was given as a 6-dose series. Research on the vaccine showed, however, that five doses are as effective as six doses in preventing anthrax. So, in November 2008, the primary series of anthrax vaccine was changed to five doses. See "Dose/Schedule" for more information.

Anthrax Vaccine Licensed for Use in the U.S.

Product: Biothrax® (Anthrax Vaccine Adsorbed)
Manufacturer: Emergent BioDefense Operations Lansing Inc
Year licensed: 1970
Product Insert

Indications Contraindications and precautions
People aged 18-65 years who are:
  • military personnel with operational or other job-related indications, such as deployment to a high threat area for 15 days or more.
  • military personnel who have received at least one dose of vaccine and wish to complete the series.
  • laboratory workers who handle cultures or animals that are infected with anthrax.
  • People who are younger than 18 years old or older than 65 years, because the vaccine is not licensed for use in these age groups.
  • People who have had a severe allergic reaction to a previous dose of anthrax vaccine or vaccine component.
  • People who are moderately or severely ill, who should wait until recovery before receiving any vaccine. Minor illnesses, such as a cold, are not a contraindication.
  • People with a possible history of latex sensitivity because the vial stopper contains dry natural rubber and may cause allergic reactions. Administer with caution to these people.
  • Women who are currently pregnant. Pregnant women should be vaccinated only if the potential benefits outweigh the potential risks to the fetus.
  • People who have a history of anthrax disease, specifically cutaneous anthrax, because this can increase the risk for severe local reactions.
  • People who are immunocompromised, including those receiving immunosuppressive therapy, because they may have a diminished immune response.
  • People with coagulation disorders or receiving medications that affect coagulation. When medically indicated, anthrax vaccine may be administered by the SQ route. Note the aluminum component of the vaccine can cause irritation of the SQ tissue.
Inadvertent vaccination during pregnancy:

Pregnant women who have received the anthrax vaccine during pregnancy should receive regular prenatal care and should discuss their anthrax vaccination with their healthcare provider and/or obstetrician. IHB has the latest information regarding pregnancy and vaccination, as well as adverse event research. IHB also offers pregnancy monitoring for women inadvertently vaccinated during pregnancy. For more information, please visit the Pregnancy page or contact IHB.

Vaccine Dose/Route Routine Administration Schedule
BioThrax Dose: 0.5 ml

Route: Intramuscular (IM) into deltoid muscle of arm. It is recommended that injections be alternated between the right and left arm.
Administer one dose at 0 weeks, 4 weeks, 6 months, 12 months, and 18 months. A booster dose should be administered every 12 months thereafter to those who remain at risk. For Service members, a booster dose is required for those deploying to a high-threat area for 15 days or more.
Note: Do NOT restart the series if a dose is late, just continue the schedule from the last dose given.
Anthrax Side Effects
  • Soreness, redness, or itching at the injection site (about 1 out of 10 men and 1 out of 6 women)
  • Lump at the injection site (about 1 out of 2 people, especially if given SQ)
  • Muscle aches or joint aches (about 1 out of 5 people)
  • Headaches (about 1 out of 5 people)
  • Fatigue (about 1 out of 15 men and 1 out of 6 women)
  • Chills or fever (about 1 out of 20 people)
  • Nausea (about 1 out of 20 people)
  • Large area of redness at the injection site (1 out of 20 people)
  • Serious allergic reactions (very rare)
Product Name Supplied Storage and Handling
BioThrax®
Emergent Biosolutions
5 mL multidose vial containing ten 0.5 mL doses Store refrigerated between 2° to 8°C (36° to 46°F). Do not freeze. Shake well before withdrawing dose from the vial. Observe for discoloration and particles. Discard if vaccine appears discolored or has visible particulate matter after shaking.

Biothrax® should appear as a milky-white suspension.
Includes AVIP key messages, current policy, the threat, the disease and the vaccine, dosage schedule and route of administration, exemptions and adverse reactions.
Includes AVIP key messages, current policy, the threat, the disease and the vaccine, dosage schedule and route of administration, exemptions, adverse reactions, storage and handling of the vaccine, and documentation.
GENADMIN PDF 21 Jun 13
III MEF FORCE HEALTH PROTECTION (FHP) REQUIREMENTS 2014
COMSEVENTHFLT PDF 20 Sep 12
IMMUNIZATION REQUIREMENTS FOR DEPLOYMENT TO SEVENTH FLEET
ANTHRAX VACCINE IMMUNIZATION PROGRAM (AVIP) UPDATE
BUMED PDF 07 Jul 10
SUSPENSION OF REGISTRATION AND MONTHLY REPORTING REQUIREMENT FOR THE ANTHRAX VACCINE IMMUNIZATION PROGRAM (AVIP)
ALARACT PDF 04 May 10
SUSPENSION OF THE ANTHRAX VACCINE IMMUNIZATION PROGRAM (AVIP) REGISTRY AND MONTHLY REPORTING REQUIREMENTS
BUMED PDF 05 Nov 09
CLINICAL POLICY FOR THE ADMINISTRATION OF THE ANTHRAX VACCINE ADSORBED (AVA) UPDATE
ALMAJCOM/SG PDF 14 Jan 09
CHANGE IN ADMINISTRATION ROUTE AND DOSING SCHEDULE FOR THE ANTHRAX VACCINE ADSORBED (AVA)
02 Jan 14

Sample Q&A: Production Issues

References: (abstracts of many of these articles can be viewed at www.ncbi.nlm.nih.gov , using the PubMed function of the National Library of Medicine)
Asa PB, Cao Y, Garry RF. Antibodies to squalene in Gulf War syndrome. Experimental & Molecular Pathology 2000;68(Feb):55-64.

Asa PB, Wilson RB, Garry RF. Antibodies to squalene in recipients of anthrax vaccine. Experimental & Molecular Pathology 2002;73(Aug):19-27.

Alving CR, Grabenstein JD. Letter to the editor. Experimental & Molecular Pathology 2000;68 (Jun):196-7 (letter).

Armed Forces Epidemiological Board. Recommendations regarding review of the paper "Antibodies to Squalene in Gulf War Syndrome" by P. B. Asa, Y. Cao and R. F. Garry. 11 Jul 2000. http://www.ha.osd.mil/afeb/reports/squalene.pdf

Asano KG, Bayne CK, Horsman KM, Buchanan MV. Chemical composition of fingerprints for gender determination. Journal of Forensic Science 2002;47(Jul):805-807.

Banzhoff A, Nacci P, Podda A. A new MF59-adjuvanted influenza vaccine enhances the immune response in the elderly with chronic diseases: Results from an immunogenicity meta-analysis. Gerontology. 2003;49(May-Jun):177-84.

Benisek Z, Suli J, Elias D, Lenhardt L, Ondrejkova A, Ondrejka R, Svrcek S, Bajova V. Experimental squalene adjuvant. II. Harmlessness and local reactogenity. Vaccine. 2004;22(Sep 3):3470-4.

Burdin N, Guy B, Moingeon P. Immunological foundations to the quest for new vaccine adjuvants. BioDrugs 2004;18(2):79-93.

Epstein JE, Charoenvit Y, Kester KE, Wang R, Newcomer R, Fitzpatrick S, Richie TL, Tornieporth N, Heppner DG, Ockenhouse C, Majam V, Holland C, Abot E, Ganeshan H, Berzins M, Jones T, Freydberg CN, Ng J, Norman J, Carucci DJ, Cohen J, Hoffman SL. Safety, tolerability, and antibody responses in humans after sequential immunization with a PfCSP DNA vaccine followed by the recombinant protein vaccine RTS,S/AS02A. Vaccine 2004;22(Apr 16):1592-603.

General Accounting Office. Questions about the presence of squalene antibodies in veterans can be resolved. GAO/NSIAD099-5, March 1999. http://www.gao.gov/archive/1999/ns99005.pdf

Hoffman SL, Edelman R, Bryan JP, Schneider I, Davis J, Sedegah M, Gordon D, Church P, Gross M, Silverman C. Safety, immunogenicity, and efficacy of a malaria sporozoite vaccine administered with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane as adjuvant. American Journal of Tropical Medicine & Hygiene 1994;51(Nov):603-12.

Institute of Medicine Committee on Health Effects Associated with Exposures During the Gulf War. Gulf War & Health: Volume I: Depleted Uranium, Sarin, Pyridostigmine Bromide, Vaccines. [Harold C. Sox, chair] Fulco CE, Liverman CT, Sox HC, editors. Washington, DC: National Academy of Sciences, September 2000. See http://stills.nap.edu/books/030907178X/html, pages 307-313 (especially 311-312).

Institute of Medicine Committee to Assess the Safety and Efficacy of the Anthrax Vaccine. The Anthrax Vaccine: Is it Safe? Does it Work? [Brian L. Strom, chair] Joellenbeck LM, Zwanziger L, Durch JS, Strom BL, editors. Washington, DC: National Academy of Sciences, March 2002. See http://www.nap.edu/catalog/10310.html, especially pages 96-97 and 147.

Kuroda Y, Nacionales DC, Akaogi J, Reeves WH, Satoh M. Autoimmunity induced by adjuvant hydrocarbon oil components of vaccine. Biomed Pharmacother 2004;58(Jun):325-37.

Lorentzen JC. Identification of arthritogenic adjuvants of self and foreign origin. Scandinavian Journal of Immunology 1999;49:45-50.

Matyas GR, Wassef NM, Rao M, Alving CR. Induction and detection of antibodies to squalene. Journal of Immunologic Methods 2000;245(Nov 1):1-14. http://www.vaccines.mil/documents/library/Squalene1.pdf

Matyas GR, Rao M, Alving CR. Detection of antibodies to squalene. II. Optimization of the assay for murine antibodies. Journal of Immunologic Methods 2001;267(Sep 15):119-129. http://www.vaccines.mil/documents/library/Squalene2.pdf

Matyas GR, Rao M, Pittman PR, Burge R, Robbins IE, Wassef NM, Thivierge B, Alving CR. Detection of antibodies to squalene. III. Naturally occurring antibodies to squalene in humans and mice. Journal of Immunologic Methods 2004;286(Mar):47-67. htthttp://www.vaccines.mil/documents/library/Squalene3.pdf

Miettinen TA. Diurnal variation of cholesterol precursors squalene and methyl sterols in human plasma lipoproteins. Journal of Lipid Research 1982;23:466-73. http://www.jlr.org/cgi/reprint/23/3/466

Nikkila K, Hockerstedt K, Miettinen TA. Serum and hepatic cholestanol, squalene and noncholesterol sterols in man: A study on liver transplantation. Hepatology 1992;15:863-70.

Nitayaphan S, Khamboonruang C, Sirisophana N, Morgan P, Chiu J, Duliege AM, Chuenchitra C, Supapongse T, Rungruengthanakit K, deSouza M, Mascola JR, Boggio K, Ratto-Kim S, Markowitz LE, Birx D, Suriyanon V, McNeil JG, Brown AE, Michael RA. A phase I/II trial of HIV SF2 gp120/MF59 vaccine in seronegative Thais: Armed Forces Research Institute of Medical Sciences--Research Institute for Health Sciences Vaccine Evaluation Group. Vaccine 2000;18(Feb 14):1448-55.

Pitisuttithum P, Nitayaphan S, Thongcharoen P, Khamboonruang C, Kim J, de Souza M, Chuenchitra T, Garner RP, Thapinta D, Polonis V, Ratto-Kim S, Chanbancherd P, Chiu J, Birx DL, Duliege AM, McNeil JG, Brown AE; Thai AIDS Vaccine Evaluation Group. Safety and immunogenicity of combinations of recombinant subtype E and B human immunodeficiency virus type 1 envelope glycoprotein 120 vaccines in healthy Thai adults. Journal of Infectious Diseases 2003;188(Jul 15):219-27.

Sesardic D, Dobbelaer R. European Union regulatory developments for new vaccine adjuvants and delivery systems. Vaccine 2004;22(Jun 23):2452-6.

Sever JL, Brenner AI, Gale AD, Lyle JM, Moulton LH, West DJ. Safety of anthrax vaccine: A review by the Anthrax Vaccine Expert Committee (AVEC) of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS). Pharmacoepidemiology & Drug Safety 2002;11 (Apr-May):189-202. http://www.vaccines.mil/documents/library/AVEC_ms.pdf

Sever JL, Brenner AI, Gale AD, Lyle JM, Moulton LH, Ward BJ, West DJ. Safety of anthrax vaccine: An expanded review and evaluation of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS). Pharmacoepidemiology & Drug Safety 2004;13:in press. Epub version on Internet. http://www.vaccines.mil/documents/library/SeverArticle.pdf

Smith TJ. Squalene: Potential chemopreventive agent. Expert Opinion Investigational Drugs 2000;9(Aug):1841-8.

Spanggord RJ, Wu B, Sun M, Lim P, Ellis W. Enhancement of an analytical method for the determination of squalene in anthrax vaccine adsorbed formulations. Journal of Pharmaceutical and Biomedical Analysis 2002;29(Jun):183-193. http://www.vaccines.mil/documents/library/JPB42(2006)494-499.pdf

United States Senate, Committee on Veterans' Affairs, 105th Congress. Report of the Special Investigation Unit on Gulf War Illnesses. Chapter 3: Evaluation of Wartime Exposures, Gulf War Veteran Health Concerns and Related Research, and Unanswered Questions. Washington, DC: 1998, pages 123 and 303. http://veterans.senate.gov/Reports/siu.htm and http://veterans.senate.gov/Reports/chapt3.pdf

Vogel FR, Powell MF, Alving CR. A Compendium of Vaccine Adjuvants and Excipients, 2nd ed. Bethesda, MD: National Institute of Allergy & Infectious Diseases, 1998. http://www.niaid.nih.gov/daids/vaccine/pdf/compendium.pdf

Wang R, Epstein J, Charoenvit Y, Baraceros FM, Rahardjo N, Gay T, Banania JG, Chattopadhyay R, de la Vega P, Richie TL, Tornieporth N, Doolan DL, Kester KE, Heppner DG, Norman J, Carucci DJ, Cohen JD, Hoffman SL. Induction in humans of CD8+ and CD4+ T cell and antibody responses by sequential immunization with malaria DNA and recombinant protein. Journal of Immunology 2004;172(May 1):5561-9.

Yoshino S, Yoshino J. Recruitment of pathogenic T cells to synovial tissues of rats injected intraarticularly with nonspecific agents. Cellular Immunology 1994;158:305-313.

Related to Influenza and Other Vaccines with MF59 Adjuvant (which contains squalene as one component of the adjuvant):

DeDonato S, Granoff D, Minutello M, Lecchi G, Faccini M, Agnello M, Senatore F, Verweij P, Fritzell B, Podda A. Safety and immunogenicity of MF59-adjuvanted influenza vaccine in the elderly. Vaccine 1999;17(Aug 6):3094-101.

Frey S, Poland G, Percell S, Podda A. Comparison of the safety, tolerability, and immunogenicity of a MF59-adjuvanted influenza vaccine and a non-adjuvanted influenza vaccine in non-elderly adults. Vaccine 2003;21(Oct 1):4234-7.

Giudice GD, Fragapane E, Bugarini R, Hora M, Henriksson T, Palla E, O'Hagan D, Donnelly J, Rappuoli R, Podda A. Vaccines with the MF59 Adjuvant Do Not Stimulate Antibody Responses against Squalene. 2006. Clinical and Vaccine Immunology, Vol. 13, No. 9. http://www.vaccines.mil/documents/library/MF59.pdf

Heineman TC, Clements-Mann ML, Poland GA, Jacobson RM, Izu AE, Sakamoto D, Eiden J, VanNest GA, Hsu HH. A randomized controlled study in adults of the immunogenicity of a novel hepatitis B vaccine containing MF59 adjuvant. Vaccine 1999;17:2769-2778.

Martin JT. Development of an adjuvant to enhance the immune response to influenza vaccine in the elderly. Biologicals 1997;25:209-13.

Minutello M, Senatore F, Cecchinelli G, Bianchi M, Andreani T, Podda A, Crovari P. Safety and immunogenicity of an inactivated subunit influenza virus vaccine combined with MF59 adjuvant emulsion in elderly subjects, immunized for three consecutive influenza seasons. Vaccine 1999;17(Jan):99-104.

Podda A, Del Giudice G. MF59-adjuvanted vaccines: increased immunogenicity with an optimal safety profile. Expert Review of Vaccines 2003;2(Apr):197-203.

Podda A. The adjuvanted influenza vaccines with novel adjuvants: experience with the MF59-adjuvanted vaccine. Vaccine 2001;19(Mar 21):2673-80.

Squarcione S, Sgricia S, Biasio LR, Perinetti E. Comparison of the reactogenicity and immunogenicity of a split and a subunit-adjuvanted influenza vaccine in elderly subjects. Vaccine 2003;21(Mar 7):1268-74.
Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009
VAERS 19 Mar 14
Vaccine Adverse Event Reporting System
Did You Receive the Anthrax Vaccine While Pregnant?
Safety Review PDF 01 Jan 12
Detailed Safety Review of Anthrax Vaccine Adsorbed
Vaccine Healthcare Centers Network
What You Need to Know About Anthrax Vaccine
Did You Receive the Anthrax Vaccine While Pregnant?
Centers for Disease Control and Prevention
Recommendations of the Armed Forces Epidemiological Board (AFEB)
Recommendations of the Armed Forces Epidemiological Board (AFEB)
Recommendations of the Armed Forces Epidemiological Board (AFEB)
Recommendations of the Armed Forces Epidemiological Board (AFEB)
Recommendations of the Armed Forces Epidemiological Board (AFEB)
Recommendations of the Armed Forces Epidemiological Board (AFEB)
Recommendations of the Armed Forces Epidemiological Board (AFEB)
VAERS 19 Mar 14
Vaccine Adverse Event Reporting System
Supplemental Form for Anthrax Vaccine in Pregnancy Registry
FAV111 PDF 17 Mar 05
FAV114 PDF 17 Mar 05
FAV113 PDF 22 Feb 05
FAV112 PDF 15 Feb 05
FAV109 PDF 30 Dec 04
FAV110 PDF 30 Dec 04
FAV107 PDF 27 Dec 04
Package Insert - Vaccine
VAERS 19 Mar 14
Vaccine Adverse Event Reporting System
Centers for Disease Control and Prevention
Department of Health and Human Services
Anthrax Vaccine Information
BioThrax
Anthrax eTool - Protecting the Worksite against Anthrax
MMQC-14-1298 09 Apr 14
Availability of the New Anthrax Trifold Brochure
MMQC-12-1518 27 Aug 12
RECEIPT OF THE NEW ANTHRAX TRIFOLDS
MMQC-12-1379 18 Jun 12
ANTHRAX VACCINE EXPIRATION NOTIFICATION FOR FAV304
MMQC-12-1376 15 Jun 12
ANTHRAX VACCINE EXPIRATION NOTIFICATION FOR FAV297
MMQC-12-1345 04 Jun 12
ANTHRAX VACCINE TWO WEEK NOTIFICATION FOR LOT FAV304
MMQC-12-1341 01 Jun 12
ANTHRAX VACCINE TWO WEEK NOTIFICATION FOR LOT FAV297
MMQC-12-1311 18 May 12
ANTHRAX VACCINE EXPIRATION 30-DAY NOTICE LOT FAV304
What You Need to Know About Anthrax Vaccine
Did You Receive the Anthrax Vaccine While Pregnant?
Safety Review PDF 01 Jan 12
Detailed Safety Review of Anthrax Vaccine Adsorbed
Vaccine Healthcare Centers Network
Vaccine Information Statement
Includes AVIP key messages, current policy, the threat, the disease and the vaccine, dosage schedule and route of administration, exemptions, adverse reactions, storage and handling of the vaccine, and documentation.
Includes AVIP key messages, current policy, the threat, the disease and the vaccine, dosage schedule and route of administration, exemptions and adverse reactions.
Safety Review PDF 01 Jan 12
Detailed Safety Review of Anthrax Vaccine Adsorbed
Vaccine Information Statement
Anthrax Vaccine Package Insert Change
FAV183 PDF 04 Apr 07
FAV188 PDF 13 Mar 07
FAV186 PDF 01 Mar 07
FAV181 PDF 22 Feb 07
FAV182 PDF 22 Feb 07
FAV184 PDF 07 Feb 07
VIS
Vaccine Information Statement
Author(s): Bradley JS, Peacock G, Krug SE, Bower WA, Cohn AC, Meaney-Delman D, Pavia AT and AAP Committee on Infectious Diseases and Disaster Preparedness Adviso
Publication: American Academy of Pediatrics
Subject: Vaccine-General
Disease: 
Anthrax
Category: 
Clinical
Author(s): ACIP
Publication: MMWR, vol. 59, no. RR-6
Subject: Vaccine-General
Disease: 
Anthrax
Author(s): Grunow R, Klee SR, Beyer W, George M, Grunow D, Barduhn A, Klar S, Jacob D, Elschner M, Sandven P, Kjerulf A, Jensen JS, Cai W, Zimmermann R, Schaad
Publication: Eurosurveillance
Subject: Disease
Disease: 
Anthrax
Author(s): Food & Drug Administration
Publication: Federal Register 2005;70,242:75180
Subject: Vaccine-General
Disease: 
Anthrax