Anthrax

Malignant Pustule, Malignant

Edema, Woolsorters Disease,
Ragpickers Disease, Maladi
Charbon, Splenic Fever

Overview

Organism
History
Epidemiology
Transmission
Disease in Humans
Disease in Animals
Prevention and Control
Center for Food Security and Public Health, Iowa State University, 2008

The Organism

The Organism

Bacillus anthracis
Large, Gram positive,
non-motile rod
Vegetative form
and spores
Nearly worldwide
distribution
Over 1,200 strains
Center for Food Security and Public Health, Iowa State University, 2008

The Spore

Sporulation requires
Poor

nutrient conditions
Presence of oxygen

Spores
Very

resistant to extremes
Survive for decades
Taken up by host and germinate

Lethal dose 2,500 to 55,000 spores

Center for Food Security and Public Health, Iowa State University, 2008

History

2001 Anthrax Letters

Center for Food Security and Public Health, Iowa State University, 2008

Center for Food Security and Public Health, Iowa State University, 2008

Transmission

Human Transmission

Industry
Tanneries
Textile

mills
Wool sorters
Bone processors
Slaughterhouses

Center for Food Security and Public Health, Iowa State University, 2008

Human Transmission

Cutaneous
Contact

with infected
tissues, wool, hide, soil
Biting flies

Inhalational
Tanning

hides,
processing wool or bone

Gastrointestinal
Undercooked

meat
Center for Food Security and Public Health, Iowa State University, 2008

Animal Transmission

Most commonly infected by

ingestion from contaminated soil or
contaminated feed or bone meal

Center for Food Security and Public Health, Iowa State University, 2008

Epidemiology

20,000-100,000 cases estimated globally/year

http://www.vetmed.lsu.edu/whocc/mp_world.htm

Center for Food Security and Public Health, Iowa State University, 2008

Anthrax in U.S.

Cutaneous anthrax
Early

1900s: 200 cases annually

Late 1900s: 6 cases annually

Inhalational anthrax
20th

century: 18 cases/16 fatal

Center for Food Security and Public Health, Iowa State University, 2008

Anthrax in the U.S.

Outbreaks - soil of endemic areas
Alkaline soil
Anthrax weather

Wet

spring that leads to grass kill

followed by hot, dry period in summer
or fall

Grass or vegetation damaged by

flood-drought sequence
Center for Food Security and Public Health, Iowa State University, 2008

Disease in Humans

Human Disease

Three forms
Cutaneous
Inhalational
Gastrointestinal

Center for Food Security and Public Health, Iowa State University, 2008

Anthrax Disease Process

Cutaneous Anthrax

95% of all cases globally

Incubation: 2-3 days (up to 12 days)
Spores enter skin through open
wound or abrasion
Papule progresses to black eschar
Severe edema
Fever and malaise
Center for Food Security and Public Health, Iowa State University, 2008

Day 2

Day 4

Day 6
Center for Food Security and Public Health, Iowa State University, 2008

Day 4

Day 6
Center for Food Security and Public Health, Iowa State University, 2008

Cutaneous Anthrax
Case fatality rate 5-20%
Untreated septicemia and death
Edema can lead to death from
asphyxiation

Day 10
Center for Food Security and Public Health, Iowa State University, 2008

Biologic Agent Case

Another family brings

in their adolescent
daughter for evaluation
of a bad infection
Surrounding facial
edema is
uncomfortable/painful
The developing eschar
is relatively painless

Cutaneous Anthrax

Cutaneous Anthrax

Inhalational Anthrax Clinical

Features

Initially starts with a nonspecific flu-like illness

and then progresses to:
Respiratory Distress
Shock

May see a widened

mediastinum on x-ray

Center for Food Security and Public Health, Iowa State University, 2008

Anthrax Hemorrhagic
Meningitis

Anthrax: Cutaneous

Left, Forearm lesion on day 7vesiculation and ulceration of initial

macular or papular anthrax skin lesion. Right, Eschar of the neck on
day 15 of illness, typical of the last stage of the lesion. From Binford
CH, Connor DH, eds. Pathology of Tropical and Extraordinary Diseases.
Vol 1. Washington, DC: AFIP; 1976:119. AFIP negative 71-12902.

Anthrax: Cutaneous

NEJM 1999; 341: 815 826

Anthrax: Cutaneous

Anthrax: Cutaneous
Notice the edema
and typical lesions

Anthrax: Cutaneous
Vesicle
development
Day 2

Day 6
Day 4

Day 10

Eschar
formation

Mediastinal Widening and Pleural

Effusion on Chest X-Ray in Inhalational
Anthrax

Gastrointestinal Anthrax

Severe gastroenteritis
Incubation:

2-5 days after consumption

of undercooked, contaminated meat

Case fatality rate: 25-75%

GI anthrax never documented in U.S.

Suspected

cases in 2000

Center for Food Security and Public Health, Iowa State University, 2008

Inhalational Anthrax
Incubation: 1-7 days (highly variable)
Initial phase

Nonspecific

- Mild fever, malaise

Second phase
Severe

respiratory distress
Dyspnea, stridor, cyanosis, mediastinal
widening, death in 24-36 hours

Case fatality: 75-90% (untreated)

Center for Food Security and Public Health, Iowa State University, 2008

Center for Food Security and Public Health, Iowa State University, 2008

Center for Food Security and Public Health, Iowa State University, 2008

Diagnosis in Humans

Isolation of B. anthracis
Blood,

skin
Respiratory secretions

Serology
ELISA
Nasal swabs

Screening

tool

Center for Food Security and Public Health, Iowa State University, 2008

Center for Food Security and Public Health, Iowa State University, 2008

B. anthracis:
Presumptive Identification
Clinical specimen (blood, CSF, etc.)
Gram stain
Capsule production

Isolate on SBA
Colony morphology
Hemolysis
Motility
Gram stain
Spores
Malachite green

B. anthracis:
Confirmatory Identification
Isolate
Phage
lysis

Capsule
Horse
blood

(MFadyean
Stain)

Bicarbonate
media

(MFadyean stain
India ink stain)

DFA
Capsule antigen
Cell wall

B. anthracis
Gram-positive, spore-forming, non-motile bacillus

Diagnosis in Humans

Anthrax quick ELISA test

New

test approved by FDA on June 7th,

2004.
Detects antibodies produced during
infection with Bacillus anthracis
Quicker and easier to interpret than
previous antibody testing methods

Results in less than ONE hour

Center for Food Security and Public Health, Iowa State University, 2008

Treatment

Penicillin
Has

been the drug of choice

Some strains resistant to penicillin and
doxycycline

Ciprofloxacin
Chosen

as treatment of choice in 2001

No strains known to be resistant

Doxycycline may be preferable

Center for Food Security and Public Health, Iowa State University, 2008

Treatment
Cutaneous Anthrax

without systemic signs, extensive edema

or lesions located on head and neck.
Initial recommended treatment:

Doxycycline or Ciprofloxacin PO for 60 days

Treatment
Cutaneous Anthrax

with systemic signs,

extensive edema or lesions
on the head and neck.

Initial recommended treatment:

Doxycycline or Ciprofloxacin IV
May switch to PO when clinically appropriate

Prevention and Control

Humans protected by preventing

disease in animals

Veterinary supervision
Trade restrictions

Improved industry standards

Safety practices in laboratories
Post-exposure antibiotic prophylaxis

Center for Food Security and Public Health, Iowa State University, 2008

Vaccination
Cell-free filtrate
Licensed in 1970
At risk

Wool

mill workers
Veterinarians
Lab workers
Livestock handlers
Military personnel
Center for Food Security and Public Health, Iowa State University, 2008

Vaccine Side Effects

Injection site reactions

Mild:

30% men, 60% women

Moderate:1-5%
Large local:1%

5-35% experience systemic effects

Muscle

or joint aches, headache, rash,

chills, fever, nausea, loss of appetite,
malaise

No long-term side effects noted

Center for Food Security and Public Health, Iowa State University, 2008

Vaccine Schedule
3 injections at two-week intervals
3 injections 6 months apart
Annual booster

Center for Food Security and Public Health, Iowa State University, 2008

Protection Against
Inhalational Anthrax
21 monkeys vaccinated at 0 and 2
weeks.
o Challenged by anthrax spores at 8
week and 38 week later: All
survived
o Challenged at 100 weeks: 88%
survived
The two doses of vaccine (0 and 2
weeks) provided protection for most
animals for almost two years

No human
post
exposure
trials have
been
documented

Center for Food Security and Public Health, Iowa State University, 2008

Vaccination

Center for Food Security and Public Health, Iowa State University, 2008

Animals and
Anthrax

Clinical Signs in Animals

Signs differ by species

Ruminants

at greatest risk

Three forms of illness

Peracute

Copyright WHO

Ruminants (cattle, sheep, goats, antelope)

Acute

Ruminants and equine

Subacute-chronic

Swine, dogs, cats

Center for Food Security and Public Health, Iowa State University, 2008

Ruminants

Peracute infection
Rapid

onset
Sudden death
Bloody discharge
from body orifices
Incomplete rigor mortis
Rapidly bloat

Center for Food Security and Public Health, Iowa State University, 2008

Ruminants

Acute infection: 1-3 days

Fever,

anorexia
Decreased rumination
Muscle tremors
Dyspnea
Abortions
Disorientation
Bleeding from orifices
Hemorrhages on internal organs
Center for Food Security and Public Health, Iowa State University, 2008

Ruminants

Chronic infection
Pharyngeal

and lingual edema

Ventral edema
Death from asphyxiation

Treatment successful if started early

Center for Food Security and Public Health, Iowa State University, 2008

Differential Diagnosis
Blackleg
Botulism
Poisoning

Plants,

heavy metal, snake bite

Lightening strike
Peracute babesiosis

Center for Food Security and Public Health, Iowa State University, 2008

Equine

Ingestion
Enteritis,

severe colic,
high fever, weakness,
death within 48-96 hours

Insect bite/vector
Hot,

painful swelling
Spreads to throat, sternum,
abdomen, external genitalia
Death

Copyright WHO

Center for Food Security and Public Health, Iowa State University, 2008

Swine
Sudden death without symptoms
Localized swelling of throat
Death by asphyxiation
Ingestion of spores

Anorexia,

enteritis

vomiting,

Center for Food Security and Public Health, Iowa State University, 2008

Dogs & Cats

Relatively resistant
Ingestion

of contaminated raw meat

Clinical signs
Fever,

anorexia, weakness
Necrosis and edema of upper GI tract
Lymphadenopathy and edema
of head and neck
Death

Due to asphyxiation, toxemia, septicemia

Center for Food Security and Public Health, Iowa State University, 2008

Diagnosis and Treatment

Necropsy not advised!
Do not open carcass!
Samples of peripheral blood needed

Cover

collection site with disinfectant

soaked bandage to prevent leakage

Treatment
Penicillin,

tetracyclines

Reportable disease
Center for Food Security and Public Health, Iowa State University, 2008

Animal Anthrax Vaccine

Recommended for livestock

in endemic areas
Sterne strain

Live encapsulated spore vaccine

Immunity in 7-10 days

Other countries use in pets and exotics
No safety or efficacy data
Adjuvant may cause reactions

Working dogs may be at risk

Center for Food Security and Public Health, Iowa State University, 2008

Animal Disease Summary

Anthrax should always be high on

differential list when
High

mortality rate in group of

herbivores
Sudden death with unclotted blood
from orifices
Localized edema

Especially neck of pigs or dogs

Center for Food Security and Public Health, Iowa State University, 2008

Prevention and
Control

Prevention and Control

Report to authorities
Quarantine the area
Do not open carcass
Minimize contact
Wear protective clothing
Latex

gloves, face mask

Center for Food Security and Public Health, Iowa State University, 2008

Prevention and Control

Burn or bury carcasses,
bedding, other materials
Decontaminate soil
Remove organic
material and
disinfect structures

Center for Food Security and Public Health, Iowa State University, 2008

Prevention and Control

Sick animals should be isolated

Scavengers should be discouraged
Insect control or repellants to
prevent fly dispersal
Prophylactic antibiotics
Vaccination
In

endemic areas
Endangered animals
Center for Food Security and Public Health, Iowa State University, 2008

Disinfection
Effective disinfection can be difficult
Prevention of sporulation best
High pressure cleaners discouraged
Soil

5%

lye or quicklime
Hydrogen peroxide, peracetic acid, or
gluteraldehyde

Bleach 1:10 dilution

May

be corrosive
Center for Food Security and Public Health, Iowa State University, 2008

Disinfection

Preliminary disinfection
10% formaldehyde
4% glutaraldehyde (pH 8.0-8.5)

Cleaning

Hot water, scrubbing, protective clothing

Final disinfection: one of the following

10% formaldehyde
4% glutaraldehyde (pH 8.0-8.5)
3% hydrogen peroxide,
1% peracetic acid

Center for Food Security and Public Health, Iowa State University, 2008

Biological Terrorism:
Estimated Effects

50 kg of spores
Urban

area of 5 million
250,000 cases of anthrax

100,000 deaths

100 kg of spores
Upwind

of Wash D.C.
130,000 to 3 million deaths

Center for Food Security and Public Health, Iowa State University, 2008

Center for Food Security and Public Health, Iowa State University, 2008