# Presentation: 544596

## National Smallpox Vaccination Program Update

- Raymond A. Strikas, M.D.
- National Immunization Program
- Centers for Disease Control and Prevention
- June 3, 2003

## Overview

- Preparedness
- Evaluation
- Compensation
- Progress to Date
- Vaccination
- Adverse events’ summary
- Challenges
- Next Steps

## 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**

## 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

## 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

## 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

## 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

## 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

## Progress to Date

## Slide 10

## Slide 11

## Slide 12

## Slide 13

## 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**

## Adverse Events following Smallpox Vaccination in Civilians

- Outline
- Adverse Event (AE) Overview
- Cardiac Adverse Events

**Notes:**
Good morning.  Thank you for the opportunity to update you on the monitoring and response to smallpox vaccine adverse events in civilians.  I will give a general adverse event overview, describe the cardiac adverse events investigation, provide data from the Active Surveillance system, and mention preliminary data from the CISA Smallpox Vaccine Study.

## 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

**Notes:**
Read slide, then...
If we compare the VAERS demographic data to that from PVS (72% revaccinees, 66% female, 72% age 40-59) we find more primary vaccinees and women in VAERS than in PVS. 

Of the 483 VAERS reports, approximately 52% hand an onset of symptoms between 7 – 30 days and 79% of those were within 7-14 days.

24% described cardiovascular events, 44% described injection site or mild systemic reactions.  Joint-related symptoms and possible hypersensitivity reactions each accounted for 5% of the reports.

##                   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 

**Notes:**
There have been no reports received of the most serious adverse events known from  historical data. 

## AE Overview VAERS/CDC Clinical Team, 1/24-5/09

| Adverse Event | Number of reports | Number confirmed |
| --- | --- | --- |
| Generalized vaccinia | 2 | 1 |
| Inadvertent inoculation, non-ocular | 13 | 4 |
| Ocular vaccinia* | 3 | 2 |

- *VIG released for one ocular vaccinia case

**Notes:**
And, only a limited number of  reports of generalized vaccinia, inadvertent inoculation and ocular vaccinia have been received. Even fewer have been confirmed by virologic testing.  

VIG has been released only once for treatment and that involved a case of ocular vaccinia.

## 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

**Notes:**
As expected, other reported serious adverse events cover a wide range of diagnoses.

## 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**

## 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

## Civilian vaccinees with ischemic events, January-May 16, 2003 

| Age (yrs) | Sex | Diagnosis | Days
Elapsed |  Medical History*
 | Outcome |
| --- | --- | --- | --- | --- | --- |
| 55 | F | MI | 5 | HTN, HL, smoker | Died |
| 57 | F | MI | 17 |  HTN, TIA, smoker | Died |
| 54 | F | MI | 10 | HTN, DM, HL, FH | Survived |
| 64 | M | MI | 2 | Exertion dyspnea | Survived |
| 46 | M | MI | 0 | Angina, HTN, DM | Survived |
| 49 | M | MI | 26 | None | Survived |
| 60 | M | Angina | 4 | Angina, HTN, HL | Survived |
| 65 | M | Angina | 10 | HTN, DM | Survived |
| 57 | M | Angina | 24 | HTN | Survived |

***CAD=Coronary Artery Disease;  HL=Hyperlipidemia; HTN=Hypertension;  DM=Diabetes Mellitus;  FH=Family History; TIA =Transient Ishemic Attack**

## 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.

**Notes:**
Read slide, then...
Although it now appears that myopericarditis may be associated with the US vaccine, it is still unclear whether post-vaccination ischemic events are causally associated.  Our investigation of both myopericarditis and ischemic events is ongoing.

## 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

## 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

## 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

**Notes:**
Based on guidance from an emergency meeting of the Advisory Committee on Immunization Practices, and consulting cardiologists, CDC modified screening critieria for potential vaccinees: persons should be excluded from the pre-event vaccination program if they have had  a diagnosis of heart disease or any type of ischemic cardiovascular disease (with or without symptoms)  OR

## 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

**Notes:**
...three or more of the following risk factors for coronary artery disease
Hypertension
Diabetes
Hypercholesterolemia
Smoking
Immediate family member with onset of heart condition onset younger than 50 years.

## 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

## 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

## 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**

## 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