Bacillus anthracis: Introduction, Microbiology and

Epidemiology, Treatment, Prevention

Anthrax

• Zoonotic disease caused by Bacillus anthracis• Infects primarily herbivores- goats, sheep,

cattle, horses and swine • Human infections - contact with infected

animals or contaminated animal products• Human infections rarely via the respiratory

or gastrointestinal tracts

Microbiology

• Bacillus anthracis - derives from Greek work for coal (anthrakis)– Disease causes black coal-like skin lesions

• B. anthracis - large Gram-positive spore-forming bacillus (1-1.5 μm x 3-10 μm)

• Grows readily on sheep blood agar

Anthrax Epidemiology

• Anthrax occurs virtually worldwide• Abundant rainfall after a period of drought

may enhance spore density in soil• Resistant spores can survive for extended

periods– 40 years in soil– 80 years in a vial– 200 years from bones from an archeological site

Friedlander A.M. 2000. Curr. Clin. Topics. Infect. Dis 20:335349

Epidemiology

• Modes of Transmission (human cases)– Contact with infected tissues of dead animals

(butchering) leading to cutaneous anthrax– Consumption of contaminated undercooked meat

leading to gastrointestional or oropharyngeal anthrax

– Contact with contaminated hair, wool or hides which can lead to either inhalational or cutaneous anthrax

Epidemiology

• Modes of Transmission (human cases)– Laboratory exposure– Person to person transmission-• Rarely reported with cutaneous anthrax

Anthrax ToxinsEdema Factor

(EF)Protective Antigen

(PA)Lethal Factor

(LF)

Edema Toxin

Lethal Toxin

MW 89,000 MW 83,000 MW 90,000

Anthrax Pathogenesis

• Infection begins with introduction of spore through the skin or mucosa

• Spore germinates into bacillus after ingestion by macrophages at the local site

• Bacillus replicates, producing toxins and capsule

• Organism can spread to the draining lymph node

Clinical Syndromes of Anthrax

• Clinical presentation varies by route of infection• Clinical syndrome:* – Cutaneous– Gastrointestinal– Oropharyngeal– Inhalation or Pulmonary/Mediastinal

• Can obviously see mixtures/combinations of above

*Meningitis can be initial presentation, but resulting from one of the described syndromes

Cutaneous Anthrax

Cutaneous Anthrax

• Most common clinical form of anthrax in natural human disease– 95% of human cases

• Caused by inoculation of spores (or bacilli?) into compromised skin

• Very low number of spores required for transmission

Cutaneous Anthrax

• Incubation period: 5 days (range 1 - 12)• Local symptoms: Painless or pruritic palpule or

pustule vesicular or ulcerative lesion black eschar

• Varying degrees of edema, may have satellite vesicles (1 - 3 mm)

Cutaneous Anthrax

• Systemic symptoms: Fever, malaise, headache, regional lymphadenopathy

• Lesion: Black eschar develops and over 2 - 3 weeks the eschar separates, leaving a scar

• Septicemia rare• Mortality if untreated: up to 20%• Mortality if treated: < 1%

Cutaneous Anthrax

Images from US CDC

http://www.bt.cdc.gov/agent/anthrax/anthrax-images/cutaneous.asp

Cutaneous Anthrax

Images from US CDChttp://www.bt.cdc.gov/agent/anthrax/anthrax-images/cutaneous.asp

Cutaneous Anthrax Management

• Antibiotics– Single drug usually adequate – may consider

multiple if evidence of bacteremia/sepsis– May not alter clinical progression of lesion, but

prevents systemic spread• Corticosteroids – controversial– Theoretical benefit in reducing edema– Most experts do not recommend routinely

• DO NOT INCISE or DEBRIDE!

Treatment of Cutaneous Anthrax Primary Treatment

• Adults: Ciprofloxacin 500mg PO BID or Doxycycline 100mg PO BID (7 - 10 days)

• Children: Ciprofloxacin 10 - 15mg/kg q 12hrs (<1gm/day)

• Pregnant women: Ciprofloxacin 500mg PO BID or Doxy (only serious)

• Immunocompromised persons: Same as above• If penicillin sensitive: Amoxicillin 80mg/kg PO TID

Gastrointestinal Anthrax

Gastrointestinal Anthrax• Transmitted by consumption of contaminated

meat– Probably ingestion of vegetative organisms

• Cannot produce disease with spores in animal models– Probably requires large inoculum of organisms

• Incubation: 1 - 6 days• Causes hemorrhagic necrotizing enteritis,

necrotizing mesenteric lymphadenitis, bacteremia/septicemia

• Case fatality rate: 25 - 60%

Anthrax: Gastrointestinal

Small bowel necrosis and necrotizing mesenteric lymphadenitis

Oropharyngeal Anthrax

Orophayngeal Anthrax

• Rare form of anthrax – Somewhat artificially separated from “lower”

gastrointestinal anthrax• Often occurs in clusters associated with

ingestion of tainted meat• Ingestion of vegetative organisms implicated– Role of ingestion of spores is debatable

Orophayngeal Anthrax

• Sometimes referred to as “cutaneous anthrax of the oropharynx”– Similar constellation of local necrotic lesion,

edema, regional adenitis– More severe systemic symptoms

• Relatively high mortality (>25%)

0 5 10 15 20Days

Incubation Period

1 to 6 days(usually 2-5 days)

Week 1 Week 2

Clinical Timeline: Oropharyngeal AnthraxEx

posu

reEx

posu

re

~ Fever~ Severe sore throat~ Severe pharyngitis~ Unilateral neck edema~ Dysphagia~ Lesion(s) in the posterior

oropharynx (often the tonsils)

~ Central necrosis and ulceration of the lesions

~ Tan or grey pseudomembrane covers the ulcer

~ Possible airway compromise

Inhalational Anthrax

Inhalational Anthrax

• Transmitted by inhalation of spore form• Incubation period 1-6 days (can be ≥ 43 days?)• Hemorrhagic meningitis seen in up to 50% of cases • GI hemorrhage in up to 80%• Mortality >85% historically

JAMA 1999;281:1735

Gram stain of blood smear in macaque with inhalational anthrax

Gram stain of cerebrospinal fluid showing B. anthracis. Emerging Infectious Diseases vol 7(6): 2001

B. anthracis from nasal swab. 24 hrs growth on sheep blood agar. Courtesy of G. Martin, MD, R. Paolucci.

Diagnosis of Anthrax• Microbiologic confirmation– Colony morphology– γ- phage lysis– DFA for cell wall and/or capsule– Biochemical testing

• Other laboratory methods– PCR – usually for pX01 and/or pX02– Serologic

• ELISA (or other method) for antigen - not widely used in US• Antibody testing – only for retrospective dx and epi

Anthrax Prevention – Infection Control

• Standard universal precautions adequate for infection control– Handwashing – Gloves – Eye protection for expected splatter

• Respiratory/droplet precautions not necessary

Anthrax Vaccine - AVA

• Given to veterinarians and laboratory workers other persons working with animal hides/products to protect against naturally occurring disease

• Given to hundreds of thousands of U.S. military personnel since 1998 to protect against the use of anthrax as a bio-weapon