1. National Smallpox Vaccination Program Update Raymond A. Strikas, M.D. National Immunization Program Centers for Disease Control and Prevention June 3, 2003

2. Overview Preparedness Evaluation Compensation Progress to Date –Vaccination –Adverse events’ summary Challenges Next Steps

3. Preparedness Smallpox program activities included in FY03 BT Guidance  Provide voluntary vaccination, follow-up service and training to those individuals who would be called upon to control and contain a smallpox outbreak  System to manage vaccination adverse events  Assessment of legal authorities  Identify and train personnel  Maintain a database of staff needed to contain an outbreak

4. Preparedness (continued) Smallpox program activities included in FY03 BT Guidance –Establish/improve rash illness surveillance and laboratory analysis to rapidly detect and investigate a smallpox outbreak Improve rash illness reporting Develop, exercise smallpox response plan Develop laboratory capacity –Assure public health has capacity to rapidly protect the public through large-scale vaccination Plan to store, manage vaccine Identify and train staff Develop, exercise large-scale vaccination plan Develop communication materials

5. Preparedness Targets for Vaccination Stage 1 – Individuals to remain targets for vaccination and training –Healthcare teams –Public health teams Numbers of individuals, teams to be determined by state, local health agencies and hospitals based on locally established preparedness goals

6. Preparedness Targets for Vaccination Stage 2 – Upon completion of Stage 1, others may be targets for vaccination, because they may support smallpox outbreak control efforts –Security staff to maintain public order –EMS staff, may include fire service personnel performing EMS duties –Hospital staff at occupational risk –Private health care providers, staff at occupational risk Numbers of individuals, teams to be determined by state, local health agencies and hospitals based on locally established preparedness goals

7. Preparedness (continued) Natural pause occurring between stages 1 and 2, as continuation guidance for CDC bioterrorism cooperative agreement implemented: –May 2 – July 1, 2003: Work plans developed –July 1 – Aug. 1, 2003: Work plans reviewed –Funds awarded by Aug. 30, 2003 –Funds support budget period Aug. 31, 2003 to Aug. 30, 2004

8. Compensation May 2003: Law in place that provides benefits to –public health team members –health care team members –public safety personnel Participating in a smallpox emergency response plan, who are injured as a result of vaccination

9. Progress to Date

14. Other Progress (from Plans) Plans approved for all states, D.C., NYC, Chicago, Los Angeles, Puerto Rico, and Palau –Public health teams: 1,154 teams 23,265 people –Healthcare teams: 4,744 teams 419,084 people

15. Adverse Events following Smallpox Vaccination in Civilians Outline –Adverse Event (AE) Overview –Cardiac Adverse Events

16. AE Overview VAERS Summary Data, 1/24 – 5/09 577 civilian reports 574 report only smallpox vaccine 57% revaccinees 77% female 61% from persons aged 40-59 years 88% non-serious

17. AE Overview VAERS and CDC Clinical Team 1/24 – 5/09 In civilian program, no reports of: Eczema vaccinatum Erythema multiforme major Fetal vaccinia Post vaccinial encephalitis or encephalomyelitis (1 suspected, see MMWR 5/23/03) Progressive vaccinia Pyogenic infection of vaccination site Vaccinia transmission to contacts

18. AE Overview VAERS/CDC Clinical Team, 1/24-5/09 Adverse EventNumber of reports Number confirmed Generalized vaccinia21 Inadvertent inoculation, non-ocular 134 Ocular vaccinia*32 *VIG released for one ocular vaccinia case

19. AE Overview Diagnoses for the Other Serious AEs, 1/24 – 5/09 Angina Anoxic encephalopathy Appendicitis Atrial fibrillation Atypical chest pain Cholecystitis Facial paralysis Headache Herpes Zoster Hypertension Myocardial infarction Neuropathy Non-cardiac chest pain Pancreatic cancer Persistent fatigue Pneumonia Premature Ventricular Contractions Sinusitis Transient global amnesia Urinary tract infection Vertigo Vomiting and diarrhea

20. Cardiac Adverse Events following Smallpox Vaccination Myopericarditis had been previously reported before 2003 –Mostly from Europe / Australia –More virulent vaccine strain used -No clear association with NYCBOH strain Ischemic events not thought to be associated with vaccination Myocarditis cases in military led to enhanced surveillance efforts in civilian program

21. Civilian Vaccinees with Myopericarditis January 24 – May 9, 2003 21 cases Ages 29-61 (median 48) 15 (71%) females Onset 1-42 d (median 12) post-vaccination 19 (90%) revaccinees All have recovered Diagnostic tests –ECG: all abnormal –Echocardiography: 6/18 abnormal –Cardiac enzymes: 1/16 abnormal

22. Civilian vaccinees with ischemic events, January-May 16, 2003 Age (yrs) SexDiagnosisDays Elapsed Medical History*Outcome 55FMI5HTN, HL, smokerDied 57FMI17 HTN, TIA, smokerDied 54FMI10HTN, DM, HL, FHSurvived 64MMI2Exertion dyspneaSurvived 46MMI0Angina, HTN, DMSurvived 49MMI26NoneSurvived 60MAngina4Angina, HTN, HLSurvived 65MAngina10HTN, DMSurvived 57MAngina24HTNSurvived *CAD=Coronary Artery Disease; HL=Hyperlipidemia; HTN=Hypertension; DM=Diabetes Mellitus; FH=Family History; TIA =Transient Ishemic Attack

23. Expected Background Rates of Incident Cardiac Events, April 4, 2003 Data from: –Atherosclerosis Risk in Communities (ARIC) –CARDIA –Framingham Offspring Cohort- 1971 –Age/gender data from vaccinees 3 week time frame- post vaccination period The actual number of acute myocardial infarction (AMI) events observed was 5. The expected number of incident AMI events during 3-weeks of follow-up observation is 2 (95% predictive interval 0.6-5.4) Data provided by the National Heart, Lung, and Blood Institute and the ARIC, Framingham Offspring and CARDIA studies.

24. Cardiac Adverse Events: What CDC is doing Rapidly developed new exclusionary criteria for potential vaccinees Investigating possible cases Conducting in-depth case-series of myocarditis and ischemic patients Developing case-definitions Developing evaluation and follow-up guidelines Evaluating other possible associations: HTN, dysrhythmias

25. Cardiac Adverse Events: What CDC is doing Completing evaluation of background rates of cardiac events Updated Active Surveillance Updating CISA Smallpox Vaccine Study Exploring ways to evaluate possible biologic mechanisms –e.g., potential prospective study might include measurement of cytokines

26. New Screening Criteria- 1 Pre-event vaccination program Persons should not receive smallpox vaccine: –Physician diagnosis of heart disease with or without symptoms Known coronary disease including MI/Angina CHF Cardiomyopathy Stroke or TIA Chest pain or shortness of breath with activity Other heart conditions under the care of a doctor

27. New Screening Criteria- 2 Pre-event vaccination program Persons should not receive smallpox vaccine: –>3 of the following risk factors for coronary artery disease Hypertension Diabetes Hypercholesteremia Current smoking Family history- before age 50

28. Smallpox Adverse Event Experience Summary AE data (esp. DoD) suggest that myopericarditis may be causally associated with smallpox vaccination Ischemic cardiac events unanticipated; causality uncertain No ischemic cardiac events reported among persons vaccinated after new exclusion criteria Few AEs historically associated with smallpox vaccine have been reported No contact transmission reported in civilian vaccination program

29. CDC Response Plan Updates Mass Casualty Guidelines Enhanced Infection Control Guidelines Environmental Control (decontamination) New and Improved! Case reporting and contact tracing forms In progress –Pediatric Issues –Threat Assessment –Incident Command

30. Challenges Threat perception low (post-Iraq conflict) Compensation law just passed, not yet implemented Assessing opportunity costs Integrating smallpox preparedness into overall bioterrorism guidance issued May 2, 2003 SARS, other competing public health priorities

31. Next Steps Continue evaluation efforts, publish findings Provide technical assistance to states in developing coop. agreement workplans Develop options for program for general public who insist on vaccination Improve PVS Determine program reporting requirments