DoD Health Care Provider’s Briefing: Anthrax Vaccine Immunization Program

1. DoD Health Care Provider’s Briefing:Anthrax Vaccine Immunization Program

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. Threat • Anthrax is one ofthe primary biological weapon (BW) threats • Evidence of production and weaponization by other countries • Northeast Asia • Southwest Asia

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. Microbiology of Anthrax • Gram positive sporulating rod

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. 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 Edema Factor (EF) MW 89,000 Protective Antigen (PA) MW 83,000 Lethal Factor (LF) MW 90,000 IncreasedCyclic AMP Local Edema Macrophage Lysis

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. Slide Of Cutaneous Ulcer

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

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. 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. CXR of Inhalational Anthrax

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. 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. 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. 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. 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

20. Picture Of Vaccination 45 o Skin Subcutaneous Tissue Muscle

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

22. Standard Interval Between Doses Between Minimum Interval • 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

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Information Sources • Chain of command • Http://www.anthrax.osd.mil • Http://www.defenselink.mil • Http://www.cdc.gov