Do D Health Care Provider s Briefing Anthrax Vaccine

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

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 Approved: 9 Jun 1999 2

Threat • Anthrax is one of the primary biological weapon (BW) threats • Evidence of production and weaponization by other countries – Northeast Asia – Southwest Asia Approved: 9 Jun 1999 3

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% Approved: 9 Jun 1999 4

Microbiology of Anthrax • Gram positive sporulating rod Approved: 9 Jun 1999 5

Epidemiology of Anthrax • Disease of herbivores • Man infected via animal products • Dramatic reduction in the U. S. since the early 1900 s • Still a problem in Asia and Africa Approved: 9 Jun 1999 6

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 Approved: 9 Jun 1999 7

Anthrax Toxin Effects Edema Factor (EF) MW 89, 000 Protective Antigen (PA) MW 83, 000 Lethal Factor (LF) MW 90, 000 Increased Cyclic AMP Local Edema Macrophage Lysis 8

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% Approved: 9 Jun 1999 9

Slide Of Cutaneous Ulcer Approved: 9 Jun 1999 10

Gastrointestinal Anthrax • Ingestion of insufficiently cooked meat from infected animals • Nausea, vomiting, fever, abdominal pain • Mortality may exceed 50% despite treatment Approved: 9 Jun 1999 11

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 Approved: 9 Jun 1999 12

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 Approved: 9 Jun 1999 13

CXR of Inhalational Anthrax Approved: 9 Jun 1999 14

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 Approved: 9 Jun 1999 15

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 Approved: 9 Jun 1999 16

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 Bio. Port Corporation (formerly known as Michigan Biologic Products Institute) Approved: 9 Jun 1999 17

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 Approved: 9 Jun 1999 18

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/antx home. htm Approved: 9 Jun 1999 19

Picture Of Vaccination 45 o Skin Subcutaneous Tissue Muscle Approved: 9 Jun 1999 20

2 weeks 4 5 months from 3 rd 5 6 months 6 6 months 18 months 3 12 months 2 6 months Dose 1 0 Vaccine Schedule • 6 shots over 18 months, then annual booster Approved: 9 Jun 1999 21

Standard Interval Between Doses • • • Between Doses 1 & 2 Doses 2 & 3 Doses 3 & 4 Doses 4 & 5 Doses 5 & 6 Approved: 9 Jun 1999 - Minimum Interval 2 weeks 5 months 6 months 22

Anthrax Vaccination Schedule • The Do. D 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 Approved: 9 Jun 1999 23

Access to Do. D 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 Do. D civilian and contract personnel – U. S. Coast Guard as applicable • Mass immunizations require prior coordination with MTF Approved: 9 Jun 1999 24

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 ongoing protection – Everyone gets some protection • Even with a good antibody response, your defense system can be overwhelmed given sufficient number of spores Approved: 9 Jun 1999 25

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 Approved: 9 Jun 1999 26

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 Approved: 9 Jun 1999 27

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 Approved: 9 Jun 1999 28

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 Approved: 9 Jun 1999 29

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 2766 C) – Yellow Shot Card (PHS-731) • Required documentation: – Date immunized, name of vaccine, manufacturer, lot number, series number, dosage, provider name and MTF address Approved: 9 Jun 1999 30

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 Approved: 9 Jun 1999 31

Adverse Event Reporting • FDA National Vaccine Adverse Event Reporting System (VAERS) – FDA and Do. D 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. Approved: 9 Jun 1999 32

Reserve Component Adverse Event Procedures • An individual experiencing a vaccine-associated adverse event in a non-duty status: – Seek medical evaluation at a Do. D 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 Approved: 9 Jun 1999 33

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 Approved: 9 Jun 1999 34

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 Approved: 9 Jun 1999 35

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 Approved: 9 Jun 1999 36

Information Sources • • Chain of command Http: //www. anthrax. osd. mil Http: //www. defenselink. mil Http: //www. cdc. gov Approved: 9 Jun 1999 37