Anthrax

Overview

Microbiology

• Gram-positive, aerobic, spore-forming bacillus

• Forms long chains ("boxcar" appearance)

• Spores are highly resistant and can survive in soil for decades

• Produces anthrax toxin (protective antigen, edema factor, lethal factor)

• Polypeptide capsule (poly-D-glutamic acid) inhibits phagocytosis

Epidemiology

• Endemic in agricultural regions: Africa, Central and South Asia, Middle East, parts of South America

• Rare in developed countries with veterinary vaccination programs

• Indonesia: sporadic cases reported, particularly in livestock farming areas

• Occupational exposure: veterinarians, livestock handlers, butchers, wool workers

• Contact with infected animals or animal products (hides, wool, bone meal)

• Laboratory workers

• Bioterrorism exposure

Transmission

1. Cutaneous (95% of natural cases): Direct contact with spores through broken skin

2. Inhalational: Inhalation of aerosolized spores

3. Gastrointestinal: Ingestion of contaminated meat

4. Injection: Contaminated drugs (heroin) - emerging route

Pathophysiology

Anthrax Toxin

• Protective Antigen (PA): Binds to cell receptors and facilitates entry

• Edema Factor (EF): Adenylate cyclase → ↑ cAMP → edema

• Lethal Factor (LF): Zinc metalloprotease → disrupts cell signaling → cell death

Disease Process

1. Spores enter body through skin, lungs, or GI tract

2. Phagocytosed by macrophages and germinate

3. Bacteria multiply and produce toxins

4. Toxins cause hemorrhage, edema, and necrosis

5. Systemic spread → septicemia → shock → death

Clinical Manifestations

1. Cutaneous Anthrax (Most Common)

• Initial: Painless, pruritic papule at inoculation site

• Vesiculation: Papule → vesicle with serosanguinous fluid

• Black eschar: Vesicle ruptures → central black necrotic ulcer ("malignant pustule")

• Surrounding edema: Extensive, non-pitting, painless edema

• Regional lymphadenopathy

• Systemic symptoms: Fever, malaise (if untreated)

• Mortality <1% with treatment

• 10-20% without treatment

2. Inhalational Anthrax ("Woolsorters' Disease")

• Non-specific flu-like symptoms

• Fever, myalgia, malaise, non-productive cough

• May have brief improvement

• Acute respiratory distress

• High fever, dyspnea, cyanosis, stridor

• Hemorrhagic mediastinitis (characteristic)

• Massive pleural effusions

• Septic shock, meningitis

• Mortality 45-85% even with treatment

• Nearly 100% without early treatment

3. Gastrointestinal Anthrax

• Oropharyngeal: Oral/esophageal ulcers, neck edema, lymphadenopathy, dysphagia

• Intestinal: Severe abdominal pain, bloody diarrhea, ascites, hematemesis

• Fever, nausea, vomiting

• Bowel perforation, peritonitis

4. Injection Anthrax

• Differs from cutaneous: more severe soft tissue infection

• No classic eschar formation

• Extensive edema, cellulitis, abscess formation

• Systemic toxicity common

Complications

• Anthrax meningitis: Hemorrhagic meningoencephalitis (50% of inhalational cases)

• Septic shock

• ARDS (Acute Respiratory Distress Syndrome)

• DIC (Disseminated Intravascular Coagulation)

• Death

Diagnosis

Clinical Suspicion

• Black eschar with painless edema

• Widened mediastinum on CXR

• Hemorrhagic pleural effusions

• Exposure history (animals, bioterrorism)

Laboratory Investigations

• Blood cultures (before antibiotics!)

• Vesicular fluid, eschar swab (cutaneous)

• Pleural fluid, CSF (if indicated)

• Stool (gastrointestinal)

• Gram stain: Large gram-positive bacilli in chains

• McFadyean reaction: Polychromatic staining of capsule

• Blood agar: Large, gray-white, non-hemolytic colonies

• "Ground glass" or "Medusa head" appearance

• PCR for B. anthracis DNA

• Rapid and specific

• Anti-protective antigen IgG (retrospective diagnosis)

Imaging

• Widened mediastinum (key finding)

• Mediastinal lymphadenopathy

• Pleural effusions (often hemorrhagic)

• Infiltrates

• No consolidation

Treatment

Antibiotics

• Ciprofloxacin 400 mg IV q12h OR Levofloxacin 750 mg IV q24h

• PLUS

• Protein synthesis inhibitor: Clindamycin 900 mg IV q8h OR Linezolid 600 mg IV q12h

• PLUS (for severe cases)

• Bactericidal agent: Meropenem 2g IV q8h OR Imipenem 1g IV q6h

• Ciprofloxacin 500 mg PO BID × 7-10 days OR

• Doxycycline 100 mg PO BID × 7-10 days

• Cutaneous: 7-10 days

• Inhalational/systemic: 60 days (switch to oral after clinical improvement)

• Meningitis: ≥ 2-3 weeks IV, consider intrathecal therapy

Adjunctive Therapy

• Raxibacumab or Obiltoxaximab (monoclonal antibodies against PA)

• For systemic anthrax, consider in conjunction with antibiotics

• Must be given early

• Aggressive fluid resuscitation

• Vasopressors for shock

• Mechanical ventilation for respiratory failure

• Drainage of pleural effusions (if needed)

Contraindications

• Avoid: Cephalosporins (intrinsic resistance), Trimethoprim-sulfamethoxazole

• Penicillin previously used but fluoroquinolones now preferred

Prophylaxis

Post-Exposure Prophylaxis (PEP)

• Confirmed or suspected exposure to B. anthracis spores

• Ciprofloxacin 500 mg PO BID × 60 days OR

• Doxycycline 100 mg PO BID × 60 days

• PLUS

• Anthrax vaccine (if available): 3 doses at 0, 2, 4 weeks

Pre-Exposure Prophylaxis

• Anthrax Vaccine Adsorbed (AVA): For high-risk groups

• Schedule: 5 doses at 0, 1, 6, 12, 18 months, then annual boosters

• Not routinely available in Indonesia

• Veterinary vaccines for livestock in endemic areas

• Key prevention strategy

Prevention

General Measures

• Proper handling of animal products

• Protective equipment for high-risk workers

• Sterilization of animal products (hides, wool)

• Vaccination of livestock in endemic areas

• Proper disposal of infected carcasses (burn, do not bury)

• Quarantine of infected herds

• Surveillance and reporting

• Education of at-risk populations

• Rapid response to outbreaks

Decontamination

• Spores resistant to many disinfectants

• Effective: Chlorine dioxide, formaldehyde, ethylene oxide, autoclaving

• Environmental decontamination requires specialized teams

Prognosis

• Cutaneous: <1% (treated), 10-20% (untreated)

• Inhalational: 45-85% (even with treatment)

• Gastrointestinal: 25-75%

• Meningitis: >90%

• Early diagnosis and treatment

• Form of disease

• Delay in antibiotic initiation

• Development of meningitis or septic shock

Key Points for Exams