The Department of Defense Smallpox Vaccination Program

1. The Department of Defense Smallpox Vaccination Program Military Vaccine Agency LTC Stephen Ford Deputy Director, Scientific Affairs 17 May 2007 UNCLASSIFIED

2. www.smallpox.milwww.vaccines.mil/smallpox

3. Background • December 2002 President directs smallpox immunization • December 16, 2002 the Department of Defense (DoD) initiates vaccination of select US forces, emergency essential civilians and contractors deployed in support of US Central Command missions • To date over 110,000 medical exemptions for contraindications in over 1.2 million Service members vaccinated

4. Program Principles: • Multi-mediaEducation: leaders, healthcare workers, and vaccinees • Screening: standardized form to identify ACIP-recognized contraindications • Adverse event monitoring: multiple communication channels, standard case definitions, pregnancy registry, long-term follow-up • Qualitystandards for immunization: before, during, and after vaccination

5. Education: Smallpox Trifold Augmented with PowerPoint slides and other training aids/materials

6. Education: Household Contacts

7. Screening: Medical Note for Contraindications

8. Monitoring: Smallpox Vaccine Pregnancy Registry

9. Monitoring: Reportable Events Joint regulation (Immunizations and Chemoprophylaxis) requires reporting of adverse events resulting in: • hospitalization • a life-threatening event (for example anaphylaxis) • time lost from duty more than 24 hours (more than 1 duty shift) • any event related to suspected contamination of a vaccine vial • any event warranting a permanent medical exemption (a contraindicating event)

10. Monitoring: Adverse Events as of 9 May 2007 • Screened: over 1.3M Vaccinated: over 1.2M • Exemption process working well • Eczema vaccinatum - 1Progressive vaccinia – 0 • VIG treatments more rare than expected • Education working well • Autoinoculation - 86 • Contact transfer vaccinia - 61: “Don’t let guard down at home.” • Case evaluation of serious adverse events: • Encephalitis – 4 • Myo-pericarditis -140 • Most vaccinia-associated myopericarditis patients experience complete resolution of MP symptoms and objective findings by 6 months • Deathsin the peri-vaccination period- 3

11. Monitoring: Adverse Events as of 9 May 2007 • Screened: over 1.3M Vaccinated: over 1.2M • Exemption process working well • Eczema vaccinatum - 1Progressive vaccinia – 0 • VIG treatments more rare than expected • Education working well • Autoinoculation - 86 • Contact transfer vaccinia - 61: “Don’t let guard down at home.” • Case evaluation of serious adverse events: • Encephalitis – 4 • Myopericarditis -140 • Most vaccinia-associated myopericarditis patients experience complete resolution of MP symptoms and objective findings by 6 months • Deaths in the post-multiple vaccination period- 2

12. Monitoring: Case Definitions (MMWR 2003;52:492-6)

13. Monitoring: DoD Cohort Studies Contrasting Vaccinated and Unvaccinated Personnel • Defense Medical Surveillance System (DMSS): • large linked database analogous to Vaccine Safety Datalink project • Includes demographic, occupational, medical encounters, immunization registry, and serial serum specimens • Lack of an association of ischemia or chest pain after smallpox vaccination (manuscript under review) • Electronic medical record Armed Forces Health Longitudinal Technology Application(AHLTA) being phased-in

14. Monitoring: DoD Commitment to Scientific Communication • DoD sharing experience with CDC, IOM, and State Health Departments (Dec ’02 to present) • First case definitions for generalized vaccinia and myocarditis • Participation on multiple working groups with CDC, ACIP, and the Defense Health Board (formerly the AFEB) • Scientific publications, such as: • Arness et al. Myopericarditis following smallpox vaccination. Am J. Epidemiol 2004;160:642-51 • Eckert et al. Incidence and follow-up of inflammatory cardiac complications following smallpox vaccination J Am Coll Cardiol 2004;44:201-5 • Barkdoll. Secondary and tertiary transfer of vaccinia virus among US personnel-United States and worldwide, 2002-2004. MMWR 2004;53:103-5. • Sejvar et al. Neurologic adverse events associated with smallpox vaccination in the US, 2002-2004. JAMA 2005;294:2744-50.

15. Vaccine Clinical Support & Consultation Services Adverse events & efficacy case management, exemptions Vaccine Safety Surveillance, reporting & adverse events registry, long term follow-up Immunization Healthcare Education For Health Care Workers & Service Members, Beneficiaries, DoD, etc. Support for Research Clinical focus, post-licensure, to “enhance vaccine safety, efficacy & acceptability” Advocacy For Quality immunization healthcare delivery Care of complex AE’s Vaccine Healthcare Center Network Network of MTF-linked Sites NOT service specific but regional Outreach & Support 24/7 Clinical Call Center (toll-free) Secure Consultative E-mail

16. Post Vaccine Pericarditis-Myocarditis-Myopericarditis Guidelines: A Work in Progress Evolving Working Group Document Based on Case Reviews & Expert Consensus Opinion

17. Knowledge, Attitudes, And Beliefs (KAB) Regarding the Vaccine Adverse Event Reporting System (VAERS) Among Department of Defense (DOD) Health Care Workers • Objectives: • To assess the knowledge, attitudes and beliefs of military health care providers regarding the identification and reporting of adverse events following immunizations (AEFI) • Convenience sample of military healthcare workers • 547 surveys distributed; 512 collected (response rate: 93.6%) • Overall, ~54% of study respondents were at least somewhat familiar with VAERS before being contacted regarding the survey • ~48% of all study participants reported having identified a patient with AEFI of any severity at least once • Of these, less than half (44.9%) reported the last identified AEFI to VAERS • Preferred method of reporting to VAERS was the VAERS web site (65.1%)

18. Smallpox Vaccination and Myopericardial Injury/Inflammation • Objectives: • To determine the rate of abnormalities in ECG and/or troponin elevation and/or other clinical indicators suggestive of symptomatic or asymptomatic myopericarditis within 30 days following influenza or smallpox vaccination • To assess changes in immune & inflammatory activation markers in a subset of vaccinees who develop indicators of either pericarditis or myocarditis & an age, gender & ethnically matched set of asymptomatic controls. • Collaborators: • Dr. Christopher Wilson, University of Washington • CDC/CISA/Kaiser • Enrollment sites: WRAMC, Fort Bragg, University of Washington: Remote civilian cases • Funding: NIAID, NIH

19. Acknowledgements • LTC (Dr.) Michael Nelson, Walter Reed Army Medical Center, Department of Allergy and Immunology • Dr. Limone Collins, Vaccine Healthcare Center Network • CDR (Dr.) Megan Ryan, Naval Health Research Center • COL (Dr.) Renata Engler, Vaccine Healthcare Center • COL Randall Anderson, Military Vaccine Agency • COL (Ret.) John Grabenstein

20. Back-up slides

21. Symptoms Criteria Any symptom in CDC case definition Any other new persistent symptom (n=0) Other new symptom affecting QOL of life attributable to vaccine by HCP (n=0) CP & fatigue most frequent Late CP usually transient & atypical for ischemia or MP recurrence of typical VAMP CP in 1-2 Nonsystematic Objective findings No persistence of clinically relevant findings Nonspecific ECG changes (normal variants) Multiple interpreters Nonsystematic Vaccinia Associated Myopericarditis Outcomes

22. Vaccinia Associated Myopericarditis OutcomesConclusions • Most VAMP patients experience complete resolution of MP symptoms and objective findings by 6 months • Up to ~30% may have nonspecific symptoms (esp. CP & fatigue) &/or ECG findings >6 months after onset of VAMP • Avoidance of activities that increase cardiovascular risk should be undertaken for at least 6 months by thesepts