Approved: 9 Jun 1999 1 DoD Health Care Provider’s Briefing: Anthrax Vaccine Immunization Program.

Approved: 9 Jun 1999 1

DoD Health Care Provider’s Briefing:

Anthrax Vaccine Immunization Program


Overview

• Anthrax is a biological weapon

• Anthrax is lethal

• Vaccine is safe and effective

• Immunization before exposure, along with wearing your mask, is critical

• This is a mandatory vaccination program, like all other force health protection vaccines


Threat

• Anthrax is one of the primary biological weapon (BW) threats

• Evidence of production and weaponization by other countries – Northeast Asia– Southwest Asia


Anthrax is an Ideal BW Agent

• Spores may survive > 40 years

• Aerosolized stable spore

• Efficient downwind spread

• Lethal dose could be inhaled with one deep breath

• Inhalational anthrax mortality reaches 100%


Microbiology of Anthrax

• Gram positive sporulating rod


Epidemiology of Anthrax

• Disease of herbivores

• Man infected via animal products

• Dramatic reduction in the U.S. since the early 1900s

• Still a problem in Asia and Africa


Pathogenesis• Spore enters skin, GI tract or lung

• Ingested by macrophages

• Transported to regional lymph nodes

• Germinate in regional nodes, mediastinum (inhalational)

• Local production of toxins

• Edema & necrosis

• Bacteremia & toxemia

• Seeding of other organ systems

Anthrax Toxin Effects

Increased Cyclic AMP

Macrophage Lysis

Edema Factor(EF)

MW 89,000

Protective Antigen(PA)

MW 83,000

Lethal Factor(LF)

MW 90,000

Local Edema


Cutaneous Anthrax

• > 95% of naturally occurring cases

• Spores enter breaks in skin after contact with contaminated animal products

• Papule - Vesicle - Ulcer - Eschar

• Up to 20% case fatality rate if untreated

• Mortality with treatment < 1%


Slide Of Cutaneous Ulcer


Gastrointestinal Anthrax

• Ingestion of insufficiently cooked meat from infected animals

• Nausea, vomiting, fever, abdominal pain

• Mortality may exceed 50% despite treatment


Inhalational Anthrax

• Incubation period 1-6 days

• Nonspecific symptoms– Malaise, fever, fatigue, cough, chest discomfort

• Terminal phase– Dyspnea, stridor, cyanosis, increased chest

pain, chest wall edema, followed by shock and death within 24-36 hours

• Meningitis seen in up to 50% of cases


Diagnosis of Inhalational Anthrax

• Initial symptoms nonspecific

• Development of respiratory distress– CXR with widened mediastinum– Usually no infiltrates

• Sputum not helpful

• Hemorrhagic pleural effusion or meningitis

• Swabs


CXR of Inhalational Anthrax


Inhalational Anthrax Treatment• Early IV antibiotics and intensive care required

– Mortality may still exceed 80%

• Penicillin - historical treatment

• Current treatment of choice:– Ciprofloxacin 400 mg IV q 8-12 h– Doxycycline 200 mg IV x 1 then 100 mg IV q 12 h

• Disease is not spread by respiratory secretions - no need for respiratory protection for health care providers– Use Standard Precautions


Post-Exposure Prophylaxis• Starting antibiotics within 24 hours after

aerosol exposure is expected to provide significant protection– Ciprofloxacin 500 mg po BID– Doxycyline 100 mg po BID

• Most effective when combined with vaccination

• Antibiotics are still indicated even when fully immunized


Anthrax Vaccine• Licensed since 1970 by the Food and Drug

Administration (FDA) – Not a new or experimental vaccine

• Sterile, cell-free (killed) bacterial vaccine – Contains predominately protective antigen from an

attenuated strain of Bacillus anthracis– Prepared from culture supernatant - there are no organisms

in the vaccine, cannot cause anthrax disease– Adsorbed to aluminum hydroxide– Contains 0.02% formaldehyde, 0.0025% benzethonium

chloride as preservatives• Manufactured by BioPort Corporation (formerly known as

Michigan Biologic Products Institute)


Vaccine Quality Control

• Each batch of any vaccine manufactured in the U.S. must meet FDA specifications and prescribed standards per 21 CFR 620– Potency, Sterility, Safety, Purity

• Testing done at manufacturer; results submitted to the FDA

• Prior to release, all stockpiled anthrax vaccine lots must pass supplemental testing


Handling Anthrax Vaccine• Vaccine must be refrigerated

• Store and maintain between 36 and 46 degrees F

• DO NOT FREEZE

• Once vial opened, use until expired– Discard if contaminated

• Reference USAMMA web site for guidance on questionable vaccine– http://www.medicine.army.mil/usamma/anthrax/

antxhome.htm


45 o

Picture Of Vaccination

Skin

Subcutaneous Tissue

Muscle


Vaccine Schedule

0

2 w

eek

s

4 w

eek

s

6 m

onth

s

12 m

onth

s

18 m

onth

s

5 months 6 months 6 monthsfrom 3rd

Dose 1 2 3 4 5 6

• 6 shots over 18 months, then annual booster


Standard Interval Between Doses

• Doses 1 & 2 - 2 weeks

• Doses 2 & 3 - 2 weeks

• Doses 3 & 4 - 5 months



Between Minimum Interval


Anthrax Vaccination Schedule

• The DoD policy is to adhere to the FDA approved vaccination schedule

• If documented gap after dose #1 is greater than two years, restart the series. Once given dose #2 or beyond, do not restart the series

• Late doses should be given ASAP - adjust timing of subsequent doses according to the standard interval schedule


Access to DoD Medical Treatment Facility (MTF)

• The following designated personnel may receive any dose at any MTF:– Active component – Reserve component (Must be in a duty status)– Emergency essential DoD civilian and contract

personnel– U.S. Coast Guard as applicable

• Mass immunizations require prior coordination with MTF


Response to Vaccine

• Anthrax vaccine, like other vaccines, stimulates your body to produce protective antibodies– Everyone has some antibody response after 2 doses– The full series is needed to obtain maximum and

on-going protection– Everyone gets some protection

• Even with a good antibody response, your defense system can be overwhelmed given sufficient number of spores


Animal Models For Human Protection

• Vaccine efficacy has been tested against numerous anthrax strains in animal studies– Guinea pigs and mice are poor animal models

for anthrax vaccine testing – Rabbits considered a more appropriate small

animal model

• Monkeys considered the best model for human response


Evidence Of Efficacy: Published Animal Trials

• 30 monkeys vaccinated twice– Challenged with aerosol at either 8, 16, 38, or

100 weeks later– 29 survived (1 died at 100 week challenge)

• 10 monkeys vaccinated once– Challenged with aerosol 6 weeks later– All survived

• Overall 98% vaccine protective efficacy


Vaccine Protection Against Different Strains

• Vaccine efficacy has been demonstrated against numerous anthrax strains in animal studies

• Biologic plausibility supports anthrax vaccine protection against all strains– Protective antigen is common to all anthrax

strains– Anthrax vaccine protection is expected against

diverse strains


Vaccine Efficacy - Inhalational Anthrax

• Human antibody response

• Animal protection data

• Compelling evidence that the vaccine series will be effective at preventing disease after an aerosol exposure


Record Keeping• Automated immunization tracking

– Service systems and DEERS central repository

• Written entries:– Health record (SF-601)– Adult Preventive and Chronic Care Flowsheet

(DD form 2766 or DD form 2766C)– Yellow Shot Card (PHS-731)

• Required documentation:– Date immunized, name of vaccine, manufacturer,

lot number, series number, dosage, provider name and MTF address


Adverse Reactions• Mild local reactions (30%)

– Redness, tenderness at site for up to 24-72 hours– Subcutaneous nodules (lumps)

• Moderate local reactions (4%)– Redness/hardness >5 cm, tenderness, itching for up to

24-72 hours• Severe local reactions rare (<1%) • Very rare systemic reactions occur (<0.2%)• Extremely rare systemic reactions (e.g., Guillain Barre

Syndrome) may occur with all vaccines


Adverse Event Reporting• FDA National Vaccine Adverse Event Reporting

System (VAERS)– FDA and DoD review 100% of adverse events reports

submitted to FDA– Anyone can submit a Form VAERS-1 – A Form VAERS-1 submission is REQUIRED for:

• Loss of duty > 24 hours

• Hospitalization

• Suspected vaccine lot contamination

– Form VAERS-1 may be obtained by calling: • 1-800-822-7967 or at www.fda.gov/cber/vaers.htm.


Reserve Component Adverse Event Procedures

• An individual experiencing a vaccine-associated adverse event in a non-duty status:– Seek medical evaluation at a DoD or civilian medical

treatment facility if necessary – Must report the event to their unit commander or

designated representative as soon as possible

• Form VAERS-1 is the same as Active Duty

• Commander will initiate Line of Duty and/or Notice of Eligibility


Contraindications• Hypersensitivity reaction to a previous dose

of anthrax vaccine or vaccine component• Younger than 18 or older than 65 • HIV positive • Temporary deferral

– Pregnancy– Active infection/illness with fever– Depressed immune response to include

corticosteroid or other immunosuppressive treatment


Pregnancy

• All vaccinations routinely deferred during pregnancy

• Before vaccination, ask all women if pregnant, defer vaccination if pregnant– Continue when no longer pregnant

• No reason to delay pregnancy or conception efforts after vaccination

• Breast feeding not a contraindication to vaccination


Conclusions

• Anthrax is a significant threat to our forces

• Anthrax vaccine is safe and effective

• Personal protective measures are still important

• Life saving benefit of anthrax vaccine make this a mandatory immunization program

• Vaccination is a crucial part of force health protection and readiness


Information Sources

• Chain of command

• Http://www.anthrax.osd.mil

• Http://www.defenselink.mil

• Http://www.cdc.gov

Approved: 9 Jun 1999 1 DoD Health Care Provider’s Briefing: Anthrax Vaccine Immunization Program.

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