# Presentation: 528809

## Rationale for Additional Post-Exposure Prophylaxis Options

**Bradley A. Perkins, M.D.**
**Meningitis & Special Pathogens Branch, **
**Division of Bacterial and Mycotic Diseases, NCID, CDC**
**Speaker 1of 4 for program “CDC Responds: Update on Options for Preventive Treatment for Persons at Risk for Inhalational Anthrax,” broadcast December 21, 2001**

## Additional Options for Those Exposed to Bacillus anthracis spores

- Earlier Recommendation - 60 days of antibiotics + medical monitoring
- Additional Option 1 - 40 additional days of antibiotic treatment + medical monitoring
- Additional Option 2 – 40 additional days of antibiotic treatment + 3 doses of anthrax vaccine over 4 weeks + medical monitoring

## Advisory Committee on Immunization Practices (ACIP) Recommendations  

**“****Use of Anthrax Vaccine in the US:  Recommendations of the [ACIP]” MMWR, December 15, 2000**
**Post-exposure prophylaxis (PEP) is recommended following aerosol exposure to *****B. anthracis***** spores**
**Antibiotics **_**>**_** 30 days if used alone, & longer therapy (up to 42 to 60 days) might be indicated**
**If anthrax vaccine is available, antibiotics can be discontinued after 3 doses of vaccine (0, 2, and 4 weeks)**

## Slide 4

## Public Health Decisions, Actions, & Options Regarding Post-Exposure Prophylaxis

- Investigational new drug (IND) application filed with FDA to use anthrax vaccine for PEP
- 60 days of antibiotics recommended for PEP
- ACIP re-convened & endorsed routine use of 60 days of antibiotics for PEP
- 217,000 doses of anthrax vaccine obtained by DHHS from DoD
- ACIP encourages provision of anthrax vaccine under IND to exposed persons

## Bioterrorism-associated Anthrax: Inhalational and Cutaneous Cases

**0**

**1**

**2**

**3**

**4**

**5**

**9/17**

**9/21**

**9/25**

**9/29**

**10/3**

**10/7**

**10/11**

**10/15**

**10/19**

**10/23**

**10/27**

**Cases**

**Date of Onset**

**NYC **
**envelopes**
**9/18***

**Senator**
**envelopes**
**10/9***

- *Postmark date of known contaminated envelopes

**Bioterrorism-associated Anthrax: Inhalational and Cutaneous Cases**

**CT inhalational anthax case, date of onset - 11/14**

## Post-Exposure Prophylaxis for Prevention of Inhalational Anthrax

- Approximately 10,000 individuals recommended to take 60 days of antibiotic therapy
- Initiated October 8 – November 25, 2001
- Primarily occupational exposures (media outlets, postal workers, congressional staffers)

## Slide 8

## Key Non-Human Primate Studies

**Henderson DW, Peacock S, Belton FC. Observations on the prophylaxis of experimental pulmonary anthrax in the monkey.  *****J Hygiene *****1956;*****54*****: 28-36.**
**Aerosol challenge: 4 & 8 LD50 (1LD50=50,000 spores)**
**Friedlander AM, Welkos SL, Pitt ML, et al. Postexposure prophylaxis against experimental inhalational anthrax. *****J Infect Dis *****1993;167: 1239-42.**
**Aerosol challenge: 8 LD50**

## Henderson DW, Peacock S, Belton FC.  Observations on the prophylaxis of experimental pulmonary anthrax in the monkey. J Hygiene 1956; 54: 28-36.

**Henderson DW, Peacock S, Belton FC.  Observations on the prophylaxis of experimental pulmonary anthrax in the monkey. *****J Hygiene *****1956; *****54*****: 28-36.**

## Henderson DW, Peacock S, Belton FC.  Observations on the 

**Henderson DW, Peacock S, Belton FC.  Observations on the **
**prophylaxis of experimental pulmonary anthrax in the monkey. *****J Hygiene *****1956; *****54*****: 28-36.**

## B. anthracis Spore Clearance 

***B. anthracis***** Spore Clearance**

**Data adapted from Henderson DW et al *****J Hygiene *****1956; *****54*****: 28-36.**

## Survival

**Survival**

**Friedlander AM, Welkos SL, Pitt ML, et al. Postexposure prophylaxis against experimental inhalational anthrax. *****J Infect Dis *****1993;167: 1239-42.**

**Notes:**
Y-axis survival rate, x-axis days post exposure
two vertical lines 1) end of abx administration, 2) test of cure

Deaths clustered at 30-60 days period

Other deaths
PCN 3 anthrax deaths days 9, 12, 20
DCN 1 anthrax death day 58
DCN + VAX 1 death day 36, no anthrax, myocardial degeneration 

## Senator Daschle & Leahy Envelopes: Postmarked 10/9/01

## Risk Assessment of Anthrax Threat Letters*

- Feb-April, 2001 @ Defence Research Establishment Suffield (DRES), Canada
- Weapons-grade *B. globigii* spores used to simulate an envelope release of *B. anthracis*
- 18x10x10 foot “office-size” chamber for release
- Extensive sophisticated aerosol sampling
- Estimated 480-3,080 LD50s in 10 min exposure

## Conclusions

- Among persons with heavy exposures to *B. anthracis* spores, 60 days of antibiotics alone may eliminate risk for inhalational anthrax
- Additional antibiotics, or antibiotic & vaccine, may benefit persons who remain at risk for inhalational anthrax after 60 days of antibiotics alone