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

2. Approved: 9 Jun 1999 2 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

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

4. Approved: 9 Jun 1999 4 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%

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

6. Approved: 9 Jun 1999 6 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

7. Approved: 9 Jun 1999 7 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

8. 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

9. Approved: 9 Jun 1999 9 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%

10. Approved: 9 Jun 1999 10 Slide Of Cutaneous Ulcer

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

12. Approved: 9 Jun 1999 12 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

13. Approved: 9 Jun 1999 13 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

14. Approved: 9 Jun 1999 14 CXR of Inhalational Anthrax

15. Approved: 9 Jun 1999 15 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

16. Approved: 9 Jun 1999 16 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

17. Approved: 9 Jun 1999 17 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)

18. Approved: 9 Jun 1999 18 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

19. Approved: 9 Jun 1999 19 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

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

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

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

23. Approved: 9 Jun 1999 23 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

24. Approved: 9 Jun 1999 24 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

25. Approved: 9 Jun 1999 25 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

26. Approved: 9 Jun 1999 26 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

27. Approved: 9 Jun 1999 27 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

28. Approved: 9 Jun 1999 28 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

29. Approved: 9 Jun 1999 29 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

30. Approved: 9 Jun 1999 30 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

31. Approved: 9 Jun 1999 31 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

32. Approved: 9 Jun 1999 32 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.

33. Approved: 9 Jun 1999 33 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

34. Approved: 9 Jun 1999 34 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

35. Approved: 9 Jun 1999 35 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

36. Approved: 9 Jun 1999 36 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

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