# Presentation: 810563

## Anthrax and Anthrax Vaccine

**Epidemiology and Prevention of Vaccine-Preventable Diseases**
**National Immunization Program**
**Centers for Disease Control and Prevention**

**Revised January 2006**

## Note: additional anthrax-related material, including images, slide sets, and vaccination and treatment recommendations are available on the CDC smallpox website at

**http://www.emergency.cdc.gov/agent/anthrax/**

## Anthrax

**Zoonotic disease caused by***** Bacillus anthracis***** **
**Described in biblical times**
**First animal vaccine developed by Louis Pasteur in 1881**
**Used for bioterrorism in 2001**

## Bacillus anthracis

**Gram-positive aerobic bacteria**
**Spores may remain viable in soil for years**
**Spores inactivated by paraformaldehyde vapor, hypochlorite, phenol, or autoclave**
**Toxins responsible for tissue damage and edema**

## Anthrax Toxins

## Anthrax Pathogenesis

**Spores enters through broken skin or mucous membranes **
**Germinate in macrophages, replicate in lymph nodes and intracellular space**
**Bacteria produce antiphagocytic capsule**
**Production of toxins cause tissue destruction and edema**

## Anthrax Pathogenesis

**Inhaled spores may reside in alveoli without germination for weeks**
**Antibiotics effective against vegetative form but not spores**
**Disease may develop after antibiotics discontinued**
**Delayed onset not described for cutaneous or gastrointestinal forms**

## Anthrax Clinical Features

**Three clinical forms**
**cutaneous (most common in natural exposure situations)**
**gastrointestinal (rare)**
**inhalation**

## Cutaneous Anthrax

**Incubation period 1-12 days**
**Papule, then vesicle, then necrotic ulcer (eschar) with ****black center**
**Usually painless**
**Case-fatality:**
**without antibiotics – 5%-20%**
**with antibiotics – <1%**

## Gastrointestinal Anthrax

**Incubation period 1-7 days**
**Pharyngeal involvement includes oropharyngeal ulcerations with cervical adenopathy and fever**
**Intestinal involvement includes abdominal pain, fever, bloody vomiting or diarrhea**
**Case-fatality estimated at 25-60%  **

## Inhalation Anthrax

**Incubation period: 1-7 days (range up to ****43 days)**
**Prodrome of cough, myalgia, fatigue, ****and fever**
**Rapid deterioration with fever, dyspnea, cyanosis and shock, often with radiographic evidence of mediastinal widening**
**Case-fatality: **
**without antibiotic treatment – 85%- 97%**
**with antibiotic treatment – 75% (45% in 2001)**

## Anthrax Laboratory Diagnosis

**Gram stain of clinical samples (skin lesion, blood, pleural fluid, CSF) **
**Culture**
**Adjunct Assays **
**PCR**
**Serology (PA based ELISA) **
**Immunohistochemistry**

## Anthrax Medical Management

**Antibiotics**
**ciprofloxacin or doxycycline and ****>1 additional drug active against *****B. anthracis********
**IV, then PO**
**30-60 days duration**
**Aggressive supportive care **

***rifampin, vancomycin, penicillin, ampicillin, chloramphenicol, **
**  ****imipenem, clincamycin, clarithromycin **

## Anthrax Epidemiology

**Reservoir****	****	****Infected animals, soil **** **
**Transmission****	****	****Direct contact (cutaneous)**
** ****	****	****	****	****	****Ingestion (gastrointestinal)**
**	****	****	****	****	****Inhalation**
**Temporal pattern****	****None**** **
**Communicability****	****Not communicable (inhalation)**
**	****	****	****	****	****very rare (cutaneous)**

## Anthrax EpidemiologyPersons at Risk

**Agricultural exposure to ****animals (rare)**
**Laboratorians exposed to *****B. anthracis***** spores (rare)**
**Processors of wool, hair, hides, bones or other animal products (extremely rare)**
**Biological terrorism**

## Anthrax—United States, 1951-2005*

***2005 provisional total**

## Anthrax Bioterrorism Attacks–United States, 2001

**22 cases (11 inhalation, 11 cutaneous) in 4 states and DC**
***B. anthracis***** sent through ****U.S. mail**
**Most exposures occurred in mail sorting facilities and sites where mail was opened**

## Bioterrorism-Related Anthrax— United States, 2001

**NYC Letters**

**DC Letter**

**September**

**October**

***MMWR***** 2001;50:941-8, 1077-9.**

**=inhalation case**

## Safe Mail Handling

**Do not open suspicious mail**
**inappropriate or unusual labeling**
**strange or no return address**
**postmark different from return address**
**excessive packaging material**
**Keep mail away from face**
**No not blow or sniff mail or mail contents**
**Wash hands after handling**
**Avoid vigorous handling (tearing, shredding)**
**Discard envelopes**

## Anthrax Vaccines

- 1881**	**** Pasteur develops first live attenuated****	**** veterinary vaccine for livestock**
- 1939**	**** Improved live veterinary vaccine**
- 1954**	**** First cell-free human vaccine**
- 1970**	**** Improved cell-free vaccine licensed **

## Anthrax Vaccine

**Cell-free culture filtrate of toxigenic strain of *****B. anthracis***
**Filtrate contains protective antigen (PA) and other cellular products**
**Adsorbed to aluminum hydroxide as an adjuvant**
**Contains small amounts of benzethonium chloride (preservative) and formaldehyde (stabilizer)**

## Anthrax Vaccine Efficacy

**95% seroconversion following ****3 doses**
**One controlled human trial using earlier vaccine**
**92.5% efficacy (cutaneous and inhalation disease combined)**
**Animal models suggest protection against inhalation anthrax**
**Duration of immunity unknown**

## Anthrax Vaccine Efficacy in Macaques

## Anthrax Vaccine Schedule

**Initial doses at 0, 2, and 4 weeks**
**Additional doses at 6, 12, and ****18 months**
**Annual booster doses thereafter**
**Alternative schedules being investigated**

## Anthrax VaccinePre-exposure Vaccination

**Persons working with production quantities or concentrations of *****B. anthracis***** cultures**
**Persons engaged in activities with a high potential for production of aerosols containing *****B. anthracis***
**Persons with increased risk of exposure to intentional release of *****B. anthracis***** (e.g., certain military personnel) **

## Anthrax VaccinePostexposure Vaccination

**No efficacy data for postexposure vaccination of humans**
**Postexposure vaccination alone not effective in animals**
**Combination of vaccine and antibiotics appears effective in animal model**

## Anthrax Postexposure Prophylaxis Vaccine Combined with Antibiotics

**Henderson, et al (1956): earlier PA-based vaccine**
**Methods:  5 days of penicillin compared to penicillin plus postexposure vaccination**
**Results:  9 of the 10 receiving just penicillin died, while all of the macaques receiving both penicillin and vaccine survived**
**Friedlander et al (1993):  aluminum hydroxide PA filtrate vaccine (current FDA-licensed vaccine)**
**Methods: 30 days of various antibiotics compared to 30 days of doxycycline  plus postexposure vaccination**
**Results: 9 of the 10 animals in the doxycycline-alone arm survived, while all receiving doxycycline and vaccine survived **

## Local reactions
 minor 				 20%-50%
 severe				 1%
Systemic symptoms	 5%-35%
Severe reactions		 rare

** ****minor ****	****	****	****	**** 20%-50%**
** ****severe****	****	****	****	**** 1%**
**Systemic symptoms****	**** 5%-35%**
**Severe reactions****	****	**** rare**

- Anthrax Vaccine Adverse Reactions

## Anthrax VaccinePrecautions and Contraindications

**Severe allergic reaction to a vaccine component or following a prior dose**
**Previous anthrax disease**
**Moderate or severe acute illness**

## Anthrax Postexposure Antibiotic Prophylaxis

**Ciprofloxicin, doxycycline, and procaine penicillin G approved for postexposure prophylaxis after aerosol exposure to *****B. anthracis***
**Due to latency of spores in lung, antibiotics should continue for 30-60 days or more**
**Discontinue antibiotics after third dose of vaccine**

** **

## Recommended Postexposure Prophylaxis to Prevent Inhalational Anthrax

**	**_Initial Therapy_**	**_Duration_
- Adults **	****Ciprofloxacin ****	****60 days**
**(including pregnant****	**** 500 mg PO BID **
**women and ****	****OR**
**immunocompromised)****	**** Doxycycline**
**	**** ****100 mg PO BID**
- Children**	****Ciprofloxacin****	**** 60 days**
** ****	****10-15 mg/kg PO Q 12 hrs*****	**
**	****OR**
**	****Doxycycline:**
**	****>8 yrs and >45 kg: 100 mg PO BID**
**	****>8 yrs and **_**<**_**45 kg: 2.2 mg/kg PO BID**
**	**_**<**_**8 yrs: 2.2 mg/kg PO BID**

***Ciprofloxacin dose should not exceed 1 gram per day in children. **

## Anthrax in Biological Terrorism

***B. anthracis***** considered likely biological terrorism threat **
**aerosolized stable spore form**
**human LD****50**** 8,000-40,000 spores (one deep breath at site of release)**
**acute illness with high fatality rate**

## Bioterrorism Information

**CDC Emergency Preparedness and Response Website**
**www.emergency.cdc.gov**

## National Immunization ProgramContact Information

**Telephone****	****    800.CDC.INFO**** **
**Email****	****	****    nipinfo@cdc.gov**** **
**Website****	****   www.cdc.gov/vaccines**