1. ANTHRAX VACCINE 14 Sep 09 Department of Defense Healthcare Provider’s
Introduction
Department of Defense
Healthcare Provider’s
Briefing
The purpose of this briefing is to introduce healthcare providers to the Anthrax Vaccine Immunization Program (AVIP). Medical personnel are the subject matter experts regarding this program.
Even if you have little involvement with vaccines in your daily practice, your patients will ask you vaccine-related questions.
Therefore, we rely on you to give good, knowledgeable answers. It is important that you become familiar with all aspects of anthrax disease and the vaccine. This briefing will cover the clinical manifestations of anthrax, the epidemiology, and current recommended treatments.
Next, I will present some facts about the vaccine, how to implement the program, and cover some frequently asked questions about the vaccine. Finally, additional references with more detailed information are listed and provided at the end of this presentation. If you oversee the administration of anthrax vaccine, be sure to become familiar with the content of the vaccine’s package insert and the clinical resources available at
ANTHRAX VACCINE
14 Sep 09

2. Dosage Schedule and Route of Administration Exemptions
Briefing Outline
Key Messages
Policy
Threat
Disease
Vaccine
Dosage Schedule and Route of Administration
Exemptions
Expected Local Adverse Reactions
Storage and Handling
Immunization Documentation
Contacts
This briefing will outline the AVIP’s key messages, information relating to current policy, the threat of the use of anthrax as a biological weapon, the disease and the vaccine, dosage Schedule and Route of Administration, exemptions, expected local adverse reactions, storage and handling of the anthrax vaccine, immunization documentation, and where to go for further information.

3. Your health and safety is our top concern
Key Messages
Your health and safety is our top concern
Receiving the vaccination is the only around-the-clock protection available for service members against this very real threat
The Food and Drug Administration says the anthrax vaccine protects against all forms of anthrax disease and is safe
Vaccination protects you, your unit, and your mission
Please remember these key messages about the DoD Anthrax Vaccine Immunization Program.
First, preserving the health and safety of our people is our top concern. What we care most about is helping our service members return home safely.
Second, the anthrax vaccine is the best protective measure against all forms of anthrax. Vaccination is the only around-the-clock protection available for service members against this very real threat.
Third, anthrax attacks would disrupt military missions. It has been extensively evaluated in human safety studies. The scientific evidence for safety and effectiveness has been affirmed by independent civilian panels, the FDA, the CDC, and the National Academy of Sciences. They all conclude that anthrax vaccine effectively protects against anthrax disease.
Finally, vaccination of military personnel is part of our national strategy to safeguard Americans against an anthrax attack. The DoD started this vaccination program based on the threat of weaponized anthrax. What we care about most is protecting our service members from known biologic threats, both natural and man-made, and keeping them healthy.
The purpose of this presentation is to provide you information regarding the danger of anthrax, the threat of anthrax as a biological weapon, and the protection and safety of the anthrax vaccine.

4. Policy History of the AVIP
Dec 97: Secretary of Defense ordered the AVIP
Mar 98: Vaccinations began in Southwest Asia
Aug 98: Vaccinations began in Korea
: Slowdowns due to shortage. After supply restored, program resumed in 2002
Oct 04: Injunction issued against DoD
Jan 05: FDA issues Emergency Use Authorization (EUA)
Dec 05: FDA formally issues Final Rule/Final Order
Oct 06: Deputy Secretary of Defense issued AVIP policy to re-establish a mandatory program for those in higher risk areas and with special roles; policy allows voluntary vaccinations for other groups
Dec 06: Under Secretary of Defense for Personnel and Readiness released DoD implementation guidance for the AVIP policy
Dec 08: Vaccine route and dosing schedule change
Let’s review the policy history of the Anthrax Vaccine Immunization Program (AVIP), because there have been several changes over the years.
In December 1997, the Secretary of Defense ordered the start of the AVIP. Vaccinations began in Southwest Asia in March 1998 and then expanded to Korea in August 1998.
A vaccine shortage caused slowdowns in 2000 and The AVIP fully resumed in Fall 2002, after the supply of FDA-licensed anthrax vaccine was restored.
A federal judge ordered an injunction in October 2004 temporarily stopping immunizations. In January 2005, vaccinations resumed under a special program called an Emergency Use Authorization (EUA).
On 19 December 2005, after extensive evaluation of the scientific literature and assessment of public comments, the FDA issued a Final Order stating that anthrax vaccine protects against all routes of anthrax exposure.
In October 2006, after a lengthy assessment of the biological threat and the vaccination program, the Deputy Secretary of Defense announced that DoD would resume mandatory anthrax vaccinations for certain groups based upon location or mission.
This new policy allows for voluntary vaccinations for those who have received one or more previous anthrax shots and wish to continue the series.
In December 2006, the Under Secretary of Defense for Personnel and Readiness released DoD implementation guidance for the AVIP policy.
And in December 2008, the FDA approves changes to route of administration and number of initial series doses of anthrax vaccine.

5. Current Policy Implementation
Mandatory and Voluntary Vaccinations
Vaccinations are mandatory for DoD service members, emergency essential designated civilians, and contractor personnel performing mission-essential services assigned to:
Central Command area of responsibility, the Korean Peninsula, and the Horn of Africa for 15 or more consecutive days
Special units with biowarfare or bioterrorism related missions
Specialty units with approved exception to policy
Vaccinations shall begin, to the extent feasible, up to 120 days prior to deployment or arrival in higher threat areas
We will now discuss the two groups covered by the AVIP policy announced by the Deputy Secretary of Defense in October Some people are subject to mandatory anthrax vaccinations and some may receive the vaccine voluntarily.
Currently, the mandatory policy applies to individuals assigned to the CENTCOM area of responsibility, the Korean peninsula, and the Horn of Africa for 15 or more consecutive days. This includes all service members, emergency essential designated civilians, contractor personnel performing mission-essential services (with the provision in their contract), some Naval Forces afloat, and civilian and contract Mariners (under Commander, Military Sealift Command).
The program is also mandatory for some personnel outside of the geographic regions of the CENTCOM AOR and the Korean peninsula – these include certain special-mission units that have a bio-warfare mission or have an approved exception to policy. These are listed in the Under Secretary of Defense for Personnel and Readiness December 2006 implementation guidance.
Vaccinations should begin, to the extent feasible, up to 120 days prior to deployment or arrival in higher threat areas to provide the greatest protection.

6. Current Policy Implementation
Vaccinations are voluntary for DoD service members who are not in the mandatory groups and have received at least one dose of Anthrax Vaccine Adsorbed during or after 1998
Vaccinations are voluntary for DoD civilians and adult family members; contractors and their accompanying US citizen family members:
Residing in Central Command area of responsibility, the Korean Peninsula, and the Horn of Africa for 15 or more consecutive days
DoD Civilian Personnel Management Service concluded notification to national unions on 12 Jan 07
The second group covered by this policy are those that may receive anthrax vaccinations voluntarily. Voluntary resumption (or continuation) of anthrax vaccine immunization is permitted for service members who received at least one previous dose of anthrax vaccine since the start of the program in 1998.
This is designed to allow individuals to continue the vaccinations on schedule when they are no longer in the designated mandatory population.
Vaccinations are voluntary for non-emergency essential DoD civilians; contractors not performing mission-essential services and accompanying US citizen family members who reside in the CENTCOM area of responsibility, Korean Peninsula, and the Horn of Africa for 15 or more consecutive days.
On 12 January 2007, the DoD Civilian Personnel Management Service provided notice to the national unions about the new civilian requirements outlined in the policy.

7. Current Policy Implementation
Ensure ALL potential vaccine recipients receive the most current educational trifold brochure available, dated 15 Jan 2009 or later
Ensure an Individual’s Briefing is available at all immunization sites
Educate potential vaccine recipients about anthrax threat and benefits, plus risks of vaccination
Screen potential vaccine recipients to confirm eligibility and potential medically exempt personnel
As a healthcare provider you will ensure ALL potential vaccine recipients receive the most current trifold brochure available, dated 15 Jan 09 or later. This is required prior to vaccination.
You will ensure an Individual’s Briefing is available at all immunization sites.
You will educate potential vaccine recipients about the anthrax threat , as well as the benefit and risks of vaccination.
You will screen potential vaccine recipients to confirm eligibility and ensure they have no medical exemptions. If a service member is found to be medically or administratively exempt it must be documented in the electronic tracking system.

8. Anthrax spores are the most likely bioweapon
Threat
Inhalation anthrax is 99% lethal if unprotected, unvaccinated, or untreated
Anthrax spores are the most likely bioweapon
Relatively easy and cheap to produce
Extremely stable – can withstand harsh environmental conditions and remain dormant up to 50 years
Can be aerosolized and delivered in a variety of methods
Odorless, colorless, tasteless, difficult to detect
The threat of anthrax is deadly and real. Inhalation anthrax is 99% lethal in unprotected, unvaccinated or untreated individuals.
Anthrax is a likely bioweapon because the bacteria forms spores with tough protective coats; allowing them to survive in the environment or in a weapon for decades.
Anthrax spores have several other characteristics that make them effective biological weapons:
The spores can be easily produced in large quantities using a basic knowledge of biology and relatively unsophisticated equipment.
The spores are extremely stable and can then be stored in a bioweapons arsenal for decades without loss of lethality.
Anthrax spores can be dispersed into the air by missiles, rockets, artillery shells, aerial bombs, sprayers from aircraft, trucks, hand-held devices, and virtually any other delivery system, including mailed packages.
Weaponized anthrax spores are odorless, colorless, tasteless, and remain difficult to detect. Therefore, it is critical to remember that protection includes vaccination and Mission Oriented Protective Posture (MOPP) gear.

9. Recognized as an illness for centuries
Anthrax Infections
Recognized as an illness for centuries
Once common where livestock were raised, now controlled using vaccine for livestock
Human infection from direct contact with infected animals, animal products, or anthrax spores
Still a problem in Asia and Africa
Terror attacks via US mail in Fall 2001
Now, let’s talk about the background of the disease. Anthrax has been documented for thousands of years, perhaps as early as the Egyptian plagues in 1500 BC. In the Middle Ages, people called anthrax the “Black Bane,” because it nearly destroyed cattle herds in Europe. In the late 1800s, scientists, such as Louis Pasteur, focused on this disease and developed the first man-made vaccine for animals.
Animals normally inhale or swallow the spores while grazing. If they inhale or swallow enough spores to become infected, they develop anthrax and eventually die. Naturally occurring anthrax has been controlled throughout the world by animal vaccination and other preventive measures, although outbreaks still occur in regions where animals are not routinely vaccinated.
In a non-Biological Warfare environment, humans become infected through agricultural or industrial exposure to contaminated animal products. This includes handling contaminated carcasses, hides, wool, hair and bones, or ingesting contaminated meat.
While cases of human anthrax infections in the U.S. have become rare, anthrax remains a problem in certain areas of Asia and Africa.
In 2006 a New York artist who created African drums from imported animal hides was diagnosed and treated for inhalation anthrax.
In 2001 the U.S. was a target of an anthrax attack via the US mail system. Eleven inhalation and eleven cutaneous case were reported in 5 states.

10. Microbiology of Anthrax
This picture is a Gram stain of Bacillus anthracis, the causative agent of anthrax.
Bacillus anthracis is a large, Gram-positive, spore-forming bacillus with a worldwide distribution. The spore forms are markedly resistant to biological extremes of heat, cold, pH, desiccation, chemicals (and thus to disinfection), irradiation and other such adverse conditions for survival in the environment for decades. The spore forms are the predominant type found in the environment. Uptake of spores is a major factor in contracting anthrax. Anthrax spores can survive in the environment for decades, awaiting uptake by the next host.
Gram-positive spore-forming rod

11. Spore enters through broken skin, gastrointestinal tract, or lung
Pathogenesis
Spore enters through broken skin, gastrointestinal tract, or lung
Ingested by macrophages
Transported to regional lymph nodes
Germinates in regional nodes
Local production of toxins cause edema & necrosis of tissue
Septicemia & toxemia
Seeding of other organ systems
Anthrax infections occur when the spores enter an opening in the body, either through a break in the skin, through ingestion of infected meat, or through inhalation.
The spores are ingested at the site of entry by macrophages, and are then transported to the regional lymph nodes, where they germinate into replicating bacteria and produce toxins.
The toxins cause edema, hemorrhage and tissue necrosis at the site. The bacteria can then spread to the blood, causing septicemia, and can also seed other organs, including the meninges. In inhalation cases, death results from a combination of respiratory failure with hemorrhagic mediastinitis, pleural effusions, overwhelming bacteremia, and often, meningitis.

12. Anthrax Toxins: Building Blocks & Effects
Edema Factor
MW 89,000
Protective Antigen
MW 83,000
Protective Antigen
MW 83,000
Lethal Factor
MW 90,000
Edema Toxin
Lethal Toxin
This slide will discuss anthrax toxins and their building blocks and effects. Anthrax bacteria produces toxins called Edema Toxin, which is comprised of edema factor and protective antigen, and lethal toxi toxin, which is comprised of lethal factor and protective antigen.
Both toxins require a protein called Protective Antigen (PA) to bind to and enter into cells in order to exert their effects.
Without the Protective Antigen, the toxins cannot form.
The Edema Toxin causes an increase in intracellular cyclic AMP, which is likely responsible for the marked edema that occurs at the site of bacterial replication.
The Lethal Toxin is directly cytolytic for the macrophages.
The Protective Antigen, which is the primary component in the US vaccine, is non-toxic. Protective Antigen is common to all anthrax strains.
Increased Cyclic AMP
Macrophage Lysis
Local Edema

13. Three types of anthrax infection
Infections
Three types of anthrax infection
Cutaneous anthrax (skin)
Gastrointestinal anthrax (GI tract)
Inhalational anthrax (lungs)
There are three types of anthrax infection: Cutaneous, gastrointestinal and inhalation.

14. Incubation period: 1-5 days
Cutaneous Anthrax
Cutaneous: Contact with spore-infected animal hides or products through a break in the skin
Incubation period: 1-5 days
Symptoms: Papule forms in 1-2 days; changes to vesicle; ruptures to form ulcer and develops black eschar (scab); lasts 2-3 weeks
Cutaneous anthrax is the most common anthrax infection seen in humans.
More than 95% of anthrax cases are cutaneous. Infection with cutaneous anthrax often occurs when a person is exposed to spores on animal products or hides, which enter through breaks in the skin. The first sign of the disease often occurs within 1-5 days after exposure. It begins as a small papule, progresses to a vesicle, ruptures to form an ulcer, followed by a black scab called an eschar (“ESS-car”), which separates after 2-3 weeks, leaving a scar.
The lesion is usually painless but may be pruritic, with varying amounts of edema surrounding it. Drugs can prevent spread but not the evolution of skin stages. With treatment, septicemic spread of the organism is uncommon, and fatality rates should be less than 1%. Untreated cutaneous anthrax infections have about a 5-20% fatality rate.

15. Gastrointestinal Anthrax
Gastrointestinal: Ingesting poorly- or undercooked infected meat
Incubation period: 2-5 days
Symptoms: Fever, abdominal pain, nausea, vomiting of blood, and bloody diarrhea
Oropharyngeal anthrax -> compromised airway
Mortality up to 25-60%
Gastrointestinal anthrax often occurs following the consumption of raw or undercooked contaminated meat.
The incubation period of gastrointestinal anthrax is approximately 2-5 days.
Symptoms consist of fever, abdominal pain, nausea, vomiting of blood, bloody diarrhea, and signs of septicemia. Involvement of the pharynx usually includes lesions at the base of the tongue, sore throat, fever, swollen lymph nodes and may result in a compromise of the oropharyngeal airway. Untreated infection may result in massive ascites and GI hemorrhage.
Gastrointestinal anthrax is a very rare disease; there were no documented US cases in the 20th century. There is a 25-60% fatality rate if the infection left untreated.

16. Incubation period: 1-6 days Symptoms:
Inhalation Anthrax
Inhalation: Spores enter lungs; ingested by macrophages, migrate to lymph nodes. Spores germinate, rapidly multiply and produce toxins
Incubation period: 1-6 days
Symptoms:
Initially flu-like: Mild fever, myalgias and malaise, cough, chest discomfort, 2-4 days
Slight improvement, hours to days
Severe respiratory distress quickly progresses to shock and death in hours to days
Toxins cause destruction of pulmonary and thoracic tissues, result in multiple organ failure
Inhalation anthrax occurs when spores enter the body through the lungs from a single deep breath. Symptoms develop within 1-6 days and resemble the common cold or flu: mild fever, muscle aches, and fatigue. Even when treated aggressively in a state-of-the-art medical facility, there is a 45-80% mortality rate. If left untreated, the fatality rate exceeds 99%.
Inhalation anthrax is not contagious.
Disease occurs when anthrax spores enter the lungs, migrate to the lymph nodes, multiply, and produce toxins.
The toxins cause bleeding and destruction of the brain or vital organs in the chest, ultimately resulting in death.
Clearly, we cannot conduct experiments using lethal agents, like anthrax, on humans. Based on limited experience with naturally-occurring anthrax we can only estimate the median lethal dose for humans. Similarly, the minimum lethal dose (the “LD1”) is unknown. Scientists estimate that you can inhale enough anthrax spores in one deep breath to kill you.
Recorded inhalation median lethal doses in non–human primates range from 2,500 to 760,000 spores. The US Department of Defense bases its strategies on an estimate that the LD50 for humans is 8,000 to 50,000 spores.
The size of an anthrax spore is anywhere from 1-5 microns.

17. Diagnosis of Inhalation Anthrax
fever
malaise
fatigue
Initial symptoms nonspecific
Development of respiratory distress
Chest X-ray with widened mediastinum
Usually no infiltrates
Sputum not helpful; spores settle in tissue
Hemorrhagic pleural effusion or meningitis
Blood cultures: Positive late in course of illness
nonspecific
The diagnosis of inhalation anthrax is very difficult, because the early symptoms, such as fever, malaise, and fatigue, are nonspecific. The most critical aspect of making the diagnosis is having a high index of suspicion. Because the presenting symptoms are so non-specific, the initial cases could easily die before the diagnosis is made, even with a high index of suspicion.
The clinical picture of respiratory distress is helpful, especially in association with chest X-ray evidence of a widened mediastinum, a result of the edema and hemorrhage occurring in the tracheobronchial lymph nodes. Note that pneumonia, with infiltrates on chest x-ray, is usually not a clinical feature with anthrax. Sputum stains and cultures may not be helpful in diagnosis, because this is a mediastinal disease and not a pneumonia. Hemorrhagic pleural effusion or hemorrhagic meningitis may be present.
Blood cultures are positive late in the course of the illness. Patients with systemic disease often die before positive blood cultures can be obtained, making early diagnosis and treatment crucial.

18. Inhalation Anthrax Treatment
Early IV antibiotics and intensive care required
Mortality may still reach 45% to 80%
Current treatment of choice (2001—multi-antibiotic therapy):
Ciprofloxacin 400 mg IV q 8-12 h
Doxycycline 200 mg IV x 1, then 100 mg IV q 12 h
Disease not spread by respiratory secretions
Use ‘Standard Precautions’
Clinical Issues
Emerging Infectious Diseases, Bioterrorism-Related Anthrax, October 2002 theme issue
Despite intensive care treatment and antibiotics, fatality rates may reach 45% to 80% after serious symptoms have occurred. Therefore, antibiotic treatment must be started at the earliest sign of disease, along with intensive care as soon as clinically indicated.
For adults, the current treatment of choice is 400mg ciprofloxacin administered intravenously every 8-12 hours, or 200mg doxycycline, administered intravenously followed by 100 mg intravenously every 12 hours. This treatment should be used unless antibiotic sensitivity of the organism is known. It is important to note that anthrax is not transmitted from person-to-person via aerosols, and respiratory isolation is not needed. As with other infections, standard (universal) precautions to include the use of gloves when handling body fluids are necessary to prevent inadvertent transmission. The vaccine is not recommended as part of the treatment for symptomatic patients.
For more information, please see the October 2002 issue of the Emerging Infectious Diseases.

19. Post-Exposure Prophylaxis
Inhalation or GI anthrax: IV ciprofloxacin or doxycycline and additional 1-2 antibiotics with activity against anthrax (60 days)
Cutaneous anthrax: Oral ciprofloxacin or doxycycline; oral penicillin used historically (60 days if suspect bioterrorism; 7-10 days natural infection)
Post-exposure prophylaxis
Oral ciprofloxacin or doxycycline (60 days)
Studies show antibiotics plus anthrax vaccine most beneficial
Antibiotics are still indicated even when fully immunized
Treat as early as suspected; intensive supportive care
Antibiotics may protect asymptomatic people after a known exposure to inhaled anthrax spores. If an anthrax exposure is highly suspected or confirmed, start oral antibiotic treatment immediately. The CDC-recommended regimen is 500 mg ciprofloxacin administered orally twice a day or the other fluoroquinolones listed on the slide for 60 days. If fluoroquinolones are not available or contraindicated, 100 mg doxycycline administered orally twice a day is recommended.
If the person has not already received at least 2 doses of anthrax vaccine, clinicians should consider continuing antibiotics until at least 2 doses of the vaccine have been received. Vaccine use post-exposure may be given under an Investigational New Drug (IND) protocol or Emergency Use Authorization (EUA). See specific guidance from responsible authorities under these circumstances.
If no vaccine is available, antibiotics should be continued for 8 weeks. If the inhaled spore quantity is potentially high, surveillance for occurrence of unexplained fever or other symptoms of late-germinating anthrax is recommended.
Even in fully immunized persons, post-exposure antibiotic treatment is indicated for four weeks, to achieve a survival rate as close to 100% as possible.

20. Licensed by the Federal government since 1970
Anthrax Vaccine Facts
Licensed by the Federal government since 1970
Administered in US to at-risk veterinarians, laboratory workers, and livestock handlers
Over 9 million doses to more than 2.3 million people since Mar 98
Vaccine primes immune system to fight anthrax
Manufactured in US by Emergent BioSolutions
“AVA,” BioThraxTM. Package insert with each vial.
Official name: Anthrax Vaccine Adsorbed
The best countermeasure against this deadly biological warfare threat is anthrax vaccine.
The Federal government licensed the current anthrax vaccine in Anthrax vaccine has been administered and proven effective when vaccinating at-risk veterinarians, laboratory workers, and livestock handlers. Over 9 million doses have been administered to more than 2.3 million people since March 1998.
This vaccine contains no whole or live anthrax bacteria; therefore, it is impossible to contract the disease from it.
Like some other vaccines, it contains aluminum hydroxide as an adjuvant to enhance its ability to stimulate antibody production, as well as benzethonium chloride as a preservative and formaldehyde as a stabilizer.
Emergent BioSolutions, formerly BioPort Corporation, is the sole manufacturer of the FDA-approved anthrax vaccine in the United States. It is not unusual that anthrax vaccine is only manufactured by one company. More than half of FDA-licensed vaccines are produced by only one manufacturer. As with all vaccines, the DoD policy is to adhere to the FDA-licensed dosing schedule as closely as possible.
Currently there is no other product that is approved by FDA to prevent anthrax before exposure.
This vaccine contains no whole or live anthrax bacteria;
therefore, it is impossible to contract the disease from it.

21. Independent Scientific Reviews
FDA Advisory Panel on Bacterial Vaccines and Toxoids
(Federal Register, 1985)
Defense Health Board (DHB), advising DoD, 1994 to present
Cochrane Collaboration, Oxford (Vaccine, 1998; 2004)
Working Group on Civilian Biodefense (JAMA, 1999, 2002)
CDC’s Advisory Committee on Immunization
Practices (ACIP) (MMWR, 2000)
Anthrax Vaccine Expert Committee (AVEC)
(Pharmacoepidemiology & Drug Safety 2002, 2004)
National Academy of Sciences (IOM), 2002
FDA Review of VAERS reports supporting FDA's Final Rule
and Final Order (2005)
Adverse events after anthrax vaccination reported to VAERS, , (Vaccine, 2009) 
Anthrax vaccine has a lengthy history of scientific evaluations. Multiple independent panels of civilian physicians and scientists have affirmed the safety and efficacy of anthrax vaccine.
In 1978, a civilian panel began advising the FDA. Their report was published in the Federal Register in 1985.
In 2002, a comprehensive, peer-reviewed report of the National Academy of Sciences and its Institute of Medicine (IOM), concluded that anthrax vaccine is effective and as safe as other vaccines. The FDA confirmed the same findings in their 2005 Final Rule and Final Order – specifically the use of the vaccine against all forms of anthrax exposure including inhalation.

22. Vaccine Efficacy in Humans
Brachman et al. Am J Public Health 1962;52:432-45
Efficacy: 92.5% (95% CI: %), jointly against cutaneous and inhalation anthrax (table 8)
Inhalation anthrax:
5 cases / 448 unvaccinated people
0 cases / 149 vaccinated people
Manufacturing improvements, 1960s CDC study
Microaerophilic, more PA, less EF and LF
Safety and efficacy reaffirmed by FDA advisory panel, Federal Register 1985; 50:
Repeated in Final Order issued by FDA, 19 Dec 05
An anthrax vaccine formulation, very similar to today’s licensed vaccine was involved in a placebo-controlled field trial. This study was conducted in a group of wool-mill workers in New Hampshire and Pennsylvania from 1955 to 1959 [Brachman, et al. Am J Publ Health 1962;52:432-45]. Cutaneous anthrax (anthrax contracted through the skin) was an occupational health hazard among wool-mill workers for many years before the study. In the Brachman study, one group of workers was vaccinated, one group received an inert placebo, and another group was simply observed. The study revealed that vaccination resulted in a statistically significant reduction in anthrax infections, compared to those not vaccinated. Vaccinated people developed disease 92.5% less often than those not vaccinated.
During the Brachman study, an outbreak of inhalation anthrax occurred at one of the four mills studied. Five cases of inhalation anthrax occurred among 448 unvaccinated people at that mill, with zero cases among 149 fully vaccinated people. Despite the obvious trend, the number of cases of inhalation anthrax was too small for the difference between groups to be statistically conclusive by itself. A follow-on study by the CDC from 1962 to 1974 reported 27 cases of cutaneous anthrax among unvaccinated (or only partially vaccinated) workers in or near the mills, compared to zero cases among those fully vaccinated.
Between 1962 and licensing in 1970, the manufacturing process was revised slightly, to give the vaccine more Protective Antigen (PA) content and make it more pure. A civilian advisory panel told the FDA in 1985 that anthrax vaccine was safe and effective and that its license should be continued. This finding appeared in the Federal Register in 1985 (
Officials from the FDA announced in a Final Order on 19 December 2005 that anthrax vaccine protects against all routes of exposure, including inhalation anthrax. After evaluating the full scientific literature and assessing comments from the public submitted in 2005, the Final Order reaffirms previous FDA conclusions that anthrax vaccine is effective in preventing anthrax from any route of exposure, including inhalation anthrax.

23. Vaccine Efficacy in Non-Human Primates
Inhalation Anthrax
55 monkeys vaccinated twice
Challenged with spore aerosol, dozens to thousands of times the median lethal dose, 8, 16, 38, or 100 wks later
52 survived. All unvaccinated control monkeys died
10 monkeys vaccinated once
Challenged with virulent spores 6 weeks later
All survived. All unvaccinated control monkeys died
Overall, 62 of 65 survived, 95% vaccine protective efficacy against inhaled anthrax spore challenge
Correlates of immunity to infer from animal to humans have not been fully developed
To show the effectiveness of the vaccine in preventing disease after an aerosol challenge, animal studies utilizing Rhesus monkeys have been performed.
In a series of studies conducted under differing conditions, 52 of 55 monkeys given two doses of anthrax vaccine were protected against a lethal aerosol challenge. An additional 10 monkeys received one dose of vaccine and then survived aerosol challenge 6 weeks later.
Overall, 62 of 65 monkeys vaccinated with the licensed anthrax vaccine survived a lethal aerosol challenge, that is a 95% survival rate; whereas all 18 unvaccinated control monkeys died.
It is important to note that correlates of immunity to infer from animal to humans have not been fully developed.
95% survival rate

24. How Anthrax Vaccine Prevents Disease
FILTER
Let’s review how anthrax vaccine protects people against anthrax disease.  Anthrax bacteria can reproduce when they come out of their hardy spores. Anthrax bacteria contain several important proteins. The most important of these proteins is called Protective Antigen, or PA for short. Other important proteins inside anthrax bacteria are called Lethal Factor (or LF) and Edema Factor (or EF).
Anthrax vaccine is made by growing a strain of anthrax bacteria that cannot cause disease. By filtering these bacteria, the vaccine will produce a filtrate that is rich in PA. The principal active ingredient in anthrax vaccine is PA.
When people get injected with small doses of anthrax vaccine, the body’s immune system responds the same as it does to all vaccines. The body makes proteins called “antibodies.” These antibodies look like the letter “Y”. The tops of those “Y”s match each different vaccine you receive. So the tops of anti-anthrax antibodies are designed to stick to the protein called PA. After vaccination, antibodies against PA circulate in the blood stream, on 24-hour patrol, ready to respond automatically to anthrax invaders.
If anthrax spores get inside your body, anthrax bacteria can emerge.  As anthrax bacteria reproduce, they make PA, LF, and EF, with potentially deadly effects. If PA combines with LF inside a person, it forms a dangerous toxin called Lethal Toxin. Lethal Toxin can cause shock and death. If PA combines with EF inside a person, it forms a dangerous toxin called Edema Toxin. Edema Toxin can cause swelling and congestion in the lungs and chest, making breathing very difficult. Remember, PA by itself is basically harmless.
For the unprotected person, anthrax bacteria can be very dangerous. But people vaccinated against anthrax have antibodies in their blood stream that neutralize PA. These antibodies attach to PA and to the PA portion of these toxins. This prevents these toxins from attacking white blood cells, preventing damage to these cells. With PA neutralized, the key protein that anthrax bacteria rely on to cause harm is locked up and out of commission. This prevents anthrax spores and bacteria from causing their deadly effects on people.
Given that all strains of anthrax bacteria produce Protective Antigen, and the US vaccine is composed primarily of Protective Antigen, the anthrax vaccine is expected by experts to protect against diverse strains, including those resistant to certain antibiotics. + =
Lethal Toxin
Anthrax vaccine is filtered,
so that it does not contain whole bacteria.
Edema Toxin = +
Therefore, anthrax vaccine
Cannot give you the disease.

25. Immunization Schedule
5 doses over 18 months
Do not compress schedule
Adjust schedule for individual delays
Do not “restart” series if it has been interrupted
; annual booster
4 weeks
6 months
12 months
18 months
150 days days days
30 days
Dose
As with all vaccines, the DoD policy is to adhere to the FDA-approved dosing schedule as closely as possible.
For anthrax vaccine, the approved immunization schedule is a dose on day 0, 4 weeks later, then at 6, 12 and 18 months after the first dose. The minimum interval between each dose is shown on the slide.
This initial five-dose series is then followed with annual boosters to maintain immunity.
Each dose of vaccine adds to protection cumulatively. The full series is needed to obtain maximum and ongoing protection.
If circumstances prevent adherence to the FDA schedule, longer intervals between doses are not expected to adversely affect antibody response.
You cannot shorten the stated time intervals between each dose. Your body needs time to build antibodies. If you get the doses too close together, you will not get the protective value of the vaccine. Don’t fall behind schedule. If you do, get vaccinated right away and get back on schedule.
Do NOT “restart” series if it has been interrupted. Even if only one dose was given or if they started many years ago, you should not restart. This recommendation follows national guidelines by the Advisory Committee on Immunization Practices (ACIP). The next dose should be given as soon as possible, with the series adjusted to conform to the standard intervals in the schedule.

26. Injection Technique Intramuscular Tissue Deltoid Area
The anthrax vaccine is administered as an intramuscular injection over the deltoid of the arm at a 90-degree angle.
Do not use nozzle jet-injector immunization devices to deliver the vaccine.
It is no longer recommended to administer the vaccine over the triceps area due to inflammation that can constrict the ulnar nerve.
Rotate arms for subsequent doses of vaccine and do not place anthrax and smallpox vaccinations in the same arm during the same visit.
Anthrax vaccine may be administered concurrently with other common immunizations, but use separate syringes and different anatomic sites.
Injection over deltoid rather than triceps is preferred, in case of swelling

27. Exemptions from Vaccination
TEMPORARY
PERMANENT
Some people should not get anthrax vaccine
Temporary medical exemptions include
Women who are pregnant, or uncertain if pregnant
Short-term immune suppression
Acute diseases, surgery
Medical evaluation or condition pending
Permanent exemptions can include
Severe allergic reaction or other serious reaction after a previous dose of anthrax vaccine
People with a history of severe latex sensitivity
HIV infection or other chronic immune deficiencies
People who had Guillain-Barré Syndrome (GBS)
Recovery from previous anthrax infection
Some people should not get anthrax vaccine or should wait to get anthrax vaccine. Let’s talk about two groups of exemptions: temporary and permanent.
Women who are pregnant are routinely deferred from most vaccinations. If a woman thinks she could be pregnant, she should get a pregnancy test prior to vaccination. A person is temporarily exempt if they are receiving treatment with certain drugs (e.g., steroid treatment >= 2 weeks), or radiation that inhibits their immune system. If they have a serious acute disease (e.g., febrile illness), or just had surgery, the physician may temporarily defer the vaccination. They may be temporarily deferred if they are currently being evaluated for a medical condition and those results are still pending. Resume vaccinations when temporary issues are resolved.
There are only a few permanent medical reasons why someone would not get anthrax vaccine. A person may be permanently exempt if they had a severe reaction to a previous dose of anthrax vaccine or are allergic to any of its components. The vial stopper contains latex which may contraindicate extraction of a vaccine dose through the stopper. People with a history of latex allergy should be referred to an allergy specialist for evaluation, unless their record provides evidence of prior consultation. Transient injection-site reactions (e.g., soreness, swelling, and nodules) should not be considered evidence of hypersensitivity.
Immunosuppressed individuals, including those who are HIV positive, should not receive the vaccine because they may not develop an adequate immune response. However, if anthrax exposure occurs, they should receive the anthrax vaccine along with antibiotics, since the vaccine would not be expected to harm them.
A permanent exemption may apply if a person has had a condition called Guillain-Barré Syndrome in the past or if there is evidence that someone has immunity to anthrax because of a previous anthrax infection. Do not give to people who have been diagnosed with lupus. They should talk with their physician about whether or not they should be vaccinated, considering the state of their disease, the medications they take, and their personal risk for specific infections. Consult medical specialists as appropriate (e.g., Vaccine Healthcare Centers Network).
Anthrax vaccine is licensed for individuals from 18 to 65 years of age. Data for safety and effectiveness are not yet available for older or younger people. Anyone falling outside of these age limits should not be vaccinated, except under guidance of a physician.
Anthrax vaccine is licensed for individuals from 18 to 65 years of age

28. Vaccinations routinely deferred during pregnancy
According to the CDC's Advisory Committee on Immunization Practices (ACIP):
“there is no convincing evidence of risk from vaccinating pregnant women with inactivated virus or bacterial vaccines or toxoids.”
Vaccinations routinely deferred during pregnancy
Before vaccination, ask each woman if she is pregnant or if there is the possibility of trying to become pregnant
No reason to delay conception after vaccination
Anthrax-vaccinated & -unvaccinated women at Fort Stewart (JAMA, 2002): same rates of conception, delivery
Anthrax-vaccinated & -unvaccinated men at fertility clinic: same sperm concentration, rate of pregnancy
Vaccination during pregnancy
Do not vaccinate pregnant women unless potential benefits of vaccination outweigh potential risk to fetus
It is DoD policy to defer routine vaccinations until after pregnancy. While routine pregnancy testing is not indicated before vaccination, respectfully ask each woman about the possibility of pregnancy. Refer women who may be pregnant for further evaluation before vaccination continues. Any woman who wishes to be tested for pregnancy will be provided one.
If a woman becomes pregnant after beginning the vaccine series, suspend the series until she is no longer pregnant. When she is no longer pregnant, the vaccine series can continue. based on a study from Fort Stewart, Georgia, there is no medical reason to delay conception after vaccination. This study contrasted anthrax-vaccinated and -unvaccinated women at Fort Stewart, and found that these groups of women had the same rate of conception and the same rate of delivery.
At the assisted reproductive technology program at Walter Reed Army Medical Center, anthrax-vaccinated and -unvaccinated men had the same sperm concentrations, motility rates, and rates of pregnancy. Regarding vaccination during pregnancy: A study suggests that anthrax vaccine may be linked with birth defects if given during pregnancy. Pregnant women should not be vaccinated against anthrax unless the potential benefits of vaccination outweigh the potential risk to the fetus.
According to the CDC's Advisory Committee on Immunization Practices (ACIP), “there is no convincing evidence of risk from vaccinating pregnant women with inactivated virus or bacterial vaccines or toxoids.”

29. Injection Site Reactions
Many may experience temporary pain and swelling after the shot
Mild side effects such as redness and tenderness at the site of vaccination are common
For both genders, IM administration significantly reduces adverse events at injection sites
Monitoring of all adverse events
Burning
Soreness
Redness
Itching
Swelling
Local pain at the injection site
As with most vaccines, many may experience temporary pain and swelling after the shot. Mild side effects such as redness and tenderness at the site of vaccination are common.
Differences in severity of side effects between men and women have been reported with anthrax vaccine; but this is consistent with differences also reported with influenza and pertussis vaccines.
Some may also experience burning, soreness, redness, itching, swelling, or local pain at the injection site. These side effects are typically not serious and should not prevent people from performing normal duties.
Sometimes an injection-site reaction will require examination by medical personnel. You may consider treating with antihistamines or topical or oral steroids such as prednisone.
A severe local reaction may result in a temporary exemption until full medical evaluation and follow-up is completed. Consult with the VHC for any other adverse events. You can call the DoD Vaccine Clinical Call Center (24/7) at
You can call the DoD Vaccine Clinical Call Center at

30. Managing Adverse Events After Any Vaccination
Minimizing injection-site reactions and systemic events
Screen for previous adverse reactions
Do not give next dose if side effects persist from previous vaccination
Issue temporary exemption if symptoms persist
Treat (and pre-treat) adverse events
Consult healthcare provider skilled in diagnosis and management of vaccine adverse events for permanent exemption
Here are some guidelines for responding to and minimizing injection-site reactions and systemic events:
Screen for previous adverse reactions to any vaccine.
Do not give the next dose if side effects persist from previous vaccination.
Issue temporary exemption if symptoms persist.
Treat and pre-treat adverse events.
Consult a healthcare provider skilled in diagnosis and management of vaccine adverse events for permanent exemption. This is a service provided by the Vaccine Healthcare Centers Network.
Clinical guidelines are available at

31. Adverse Event Reporting
When in doubt, report it!
Vaccine Adverse Event Reporting System (VAERS)
FDA and CDC review 100% of adverse-event reports
All VAERS forms reviewed by independent panel of expert civilian physicians for 4 years
DoD requires healthcare workers submit a VAERS Form for
Loss of duty 24 hours or longer
(> 1 duty day)
Hospitalization
Suspected vaccine vial contamination
Other submissions are encouraged
Anyone can submit a VAERS Form
As for reporting adverse events, when in doubt, report it.
The Vaccine Adverse Event Reporting System, referred to as VAERS, was initiated in 1990 to oversee vaccine safety issues across America. This system is managed jointly by the FDA and Centers for Disease Control and Prevention (CDC). It is a “spontaneous,” or “passive,” surveillance system. This means that it relies on healthcare professionals, guardians and patients to submit reports of adverse events following vaccination. Filing a VAERS report does not prove that the reaction was caused by the vaccine but only reflects an association.
The FDA and CDC review all adverse-event reports submitted.
A VAERS report must be submitted if any adverse event results in 24 hours or more time lost from duty or work, or if someone is hospitalized due to immunizations. Any potential contamination of vaccine lots must also be reported through VAERS. However, any vaccine-associated event may be reported through VAERS. It’s important to stress that anyone can submit a VAERS Form.
Reports to VAERS may be made in writing, via the web, or by calling toll free Reporting instructions are available on the Internet at The VHC will assist with any VAERS through the website at

32. Reserve Component Adverse Event Guidance
If someone experiences an adverse event in a non-duty status that is possibly associated with a vaccination
Should seek medical evaluation at a DoD, USCG, or civilian medical treatment facility, if necessary
Should Report the event to your unit Commander or designated representative as soon as possible
Should see local medical department or squadron for guidance
Commander will determine Line of Duty and/or Notice of Eligibility status, if required
Submit VAERS for any suspected adverse event
Adverse events after DoD or USCG-directed vaccinations are line-of-duty conditions.
Any adverse event that occurs in a Reserve Component member should be managed consistent with the Active Component requirements. If a vaccine-associated adverse event occurs in a non-duty status, the individual should seek medical care as appropriate. The individual must also report the event to the unit Commander or designated representative as soon as possible. The Commander will initiate a Line of Duty (LOD) and/or Notice of Eligibility (NOE) as appropriate. An individual, healthcare provider, or Commander may submit a VAERS report.
For information on civilian healthcare services, contact the Military Medical Support Office at ; or via the web at

33. Storage and Handling Keep anthrax vaccine refrigerated
Store between 2° to 8° C (36° to 46° F)
Temperature check twice a day, even with alarm system
Keep logs for up to three years
DO NOT FREEZE
Once vial opened, use until expiration date
Do not pre-filling vaccine into syringes
Storage devices
Medical Grade/Household refrigerator
VaxiCool or VaxiPac
The vials should be stored in a refrigerator and maintained between 2 to 8 degrees C (36 – 46 degrees F).
The refrigerator should be checked twice a day to ensure temperatures do not exceed the recommended range; even if it has an alarm system. All temperature logs should be maintained for up to 3 years.
The vaccine should never be frozen. If the product is found to be frozen, immediately segregate and label the product as potentially compromised. Then contact United States Army Medical and Materiels Agency (USAMMA) for further guidance.
According to ACIP guidelines, once a vial is opened, the vaccine can be used until the expiration date on the label, as long as it is properly stored and maintained. Pre-filling of syringes is not recommended due to possible storage and handling failures or vaccine administration errors.
Proper storage devices include medical grade refrigerators, household refrigerators with separate refrigerator/freezer compartments, or a VaxiCool. A VaxiPac can be used for short-term storage and transport.
Information can be found on the USAMMA website at

34. Automated immunization tracking (primary)
Record Keeping
Automated immunization tracking (primary)
Service systems and DEERS central repository
Do not give any vaccination more than 4 days early
Written entries
Required documentation
Deployable Medical Record; Adult Preventive & Chronic Care Flowsheet (DD Form 2766, DD Form 2766C)
Date immunized
Name of vaccine
Manufacturer
Lot number
Series number
Dosage
Vaccinator’s name
VIS date
Making sure every vaccination is correctly entered into a DoD Electronic Immunization Tracking System is vital to the success of this program and important to quality healthcare.
Do not give any vaccination more than 4 days early. Early vaccinations will not count in the series in the automated systems.
Each entry will include the date immunized, name of vaccine, manufacturer, lot number, series number, dosage, vaccinator’s name and VIS date. Entries will be made in the Service’s Automated Immunization Tracking System, the individual’s medical record, the DD-2766C and the Yellow Shot Card (CDC-731) if provided by the individual. Clinics should develop protocols to ensure quality assurance in the documentation process.

35. Anthrax spores are a lethal threat to our forces
Conclusion
Anthrax spores are a lethal threat to our forces
FDA has repeatedly said the anthrax vaccine is safe and effective
The life-saving benefits of anthrax vaccine make this an essential immunization program
For service members to understand the value of anthrax vaccination, they need your help
Make sure service members understand the anthrax vaccine dosing schedule – remind them when their next vaccination in the series is due
Expeditiously assist anyone experiencing an adverse event in getting proper medical care and advice
DoD’s anthrax immunization policy has been developed to provide military personnel with protection against one of the most significant biological threats against our forces.
The vaccine is safe and effective in protecting against anthrax disease. This has been affirmed by multiple independent panels of civilian physicians and scientists.
The life-saving benefits of anthrax vaccine make this an essential immunization program.
For service members to understand the value of anthrax vaccination, they need your help. Education helps alleviate many of the fears of the unknown. If someone is experiencing an adverse event, they may need your assistance in getting the proper medical treatment.
Remember, the health and safety of our Servicemembers is our top concern.

36. Resources MILVAX Agency www.vaccines.mil www.anthrax.mil
877.GET.VACC
DoD Vaccine Clinical Call Center
Vaccine Healthcare Centers for help with adverse event management
Information for Civilian Healthcare Providers
Call the Military Treatment Facility (MTF) where the member is enrolled OR contact the Military Medical Support Office (MMSO)
if the member is not enrolled to an MTF
USAMMA DOC
Should you need additional information, please refer to the websites or contact information listed here.

37. Closing
This concludes this block of instruction. We hope this presentation has been helpful.