Makindo Medical Notes

Early diagnosis of anthrax and the initiation of appropriate treatment, particularly the use of a combination of antimicrobial drugs, are critical to improving survival. Inhalational anthrax, in particular, requires immediate medical attention due to its high mortality rate if untreated.

About

• Anthrax is derived from the Greek word for "coal," referring to the characteristic black eschar seen in cutaneous infections.
• Caused by the spore-forming bacterium Bacillus anthracis, which primarily infects herbivores and can be transmitted to humans through contact with contaminated animal products (hides, wool, or meat).
• It is a zoonotic disease with global distribution, especially in regions where livestock vaccination is limited.

Characteristics

• Gram-positive, aerobic, spore-forming bacillus. Spores are highly resilient and can survive in harsh environments for decades.
• Encapsulated in vivo by a polypeptide capsule made of D-Glutamic acid, which is antiphagocytic, allowing the bacteria to evade the host's immune system.
• The spores germinate when they enter a host, usually through the skin, inhalation, or ingestion, leading to active infection.

Source

• Present in soil contaminated by the spores from infected animal carcasses, especially in regions with poor veterinary control and livestock vaccination.
• Commonly affects herbivorous animals such as cattle, sheep, and goats, and can be transmitted to humans through direct contact with contaminated animal products or consumption of undercooked meat.
• Anthrax is endemic in parts of:
  • Central and South America
  • Sub-Saharan Africa
  • Asia and South/Eastern Europe
  • The Caribbean
• Humans can also be exposed to anthrax spores through bioterrorism (e.g., anthrax spores sent via mail during the 2001 attacks in the US).

Virulence - Toxin Production and Capsule

• Protective antigen (PA): Binds to host cells and forms channels, allowing the entry of lethal factor (LF) and oedema factor (EF).
• Lethal factor (LF): A protease that disrupts cell signalling by cleaving mitogen-activated protein kinase (MAP kinase), resulting in cell death.
• Oedema factor (EF): A calmodulin-activated adenylate cyclase that increases intracellular cyclic AMP (cAMP), leading to fluid accumulation, oedema, and immune dysregulation.
• The combined effect of these toxins leads to severe tissue damage, oedema, haemorrhage, and immune evasion.
• The bacteria's antiphagocytic capsule allows it to evade the host's immune system, enabling the pathogen to replicate and spread.

Pathophysiology

Clinical Pathogenicity

• Cutaneous Anthrax (Most common, ~95% of cases):
  • Occurs when spores enter through skin abrasions or cuts, typically after handling animal hides, wool, or bones.
  • Begins as a small papule that progresses into a painless ulcer with a characteristic black eschar (necrotic tissue). Surrounding tissue may become swollen and inflamed.
  • Localised haemorrhagic lymphadenitis may develop as the infection progresses, and without treatment, it can become systemic.
• Inhalational Anthrax (Mortality > 50% if untreated):
  • Also known as "wool sorters' disease," this form results from inhalation of anthrax spores from contaminated animal products or bioterrorism.
  • Initial symptoms resemble a flu-like illness with fever, malaise, cough, and chest pain. This is followed by rapid progression to severe respiratory distress, cyanosis, and shock.
  • Findings on CXR include a widened mediastinum and pleural effusions due to haemorrhagic mediastinitis, often leading to death if untreated.
• Gastrointestinal Anthrax:
  • Acquired by ingesting undercooked meat from infected animals.
  • Symptoms include nausea, vomiting, abdominal pain, bloody diarrhoea, and intestinal perforation in severe cases.
  • Mortality is high if not treated promptly, as the infection can become systemic, leading to sepsis.
• Systemic Anthrax (Shock/Sepsis):
  • All forms of anthrax can progress to systemic involvement, with symptoms such as hypotension, renal failure, and disseminated intravascular coagulation (DIC).
  • Complications include microangiopathic haemolytic anaemia, thrombocytopenia, coagulopathy, haemorrhage, and meningitis.
  • Meningitis secondary to anthrax is often fatal due to haemorrhagic brain infection.

Investigations

• Microscopy: Spores can be visualized with modified Ziehl-Neelsen staining.
• McFadyen's Reaction: Demonstrates anthrax bacilli in blood samples by heat-fixing the sample with polychrome methylene blue, showing blue bacilli surrounded by pink capsular debris.
• Serology for capsular antigen can help confirm diagnosis.
• Imaging: CXR may reveal mediastinal widening in inhalational anthrax, and CT can show pleural effusions and mediastinal involvement.
• Polymerase chain reaction (PCR) and culture can confirm the presence of Bacillus anthracis, although culture may be slow.

Management: Consult Infectious Diseases Early

• Prevention: Vaccination is available for individuals at high risk, including military personnel, veterinarians, and those working with animal products in endemic areas.
• Supportive care: ABC management (Airway, Breathing, Circulation), ITU support, oxygen therapy, and IV fluids as needed.
• Antibiotic therapy: First-line: Ciprofloxacin, Levofloxacin, or Doxycycline, often combined with aminoglycosides or rifampin for synergy. If the strain is susceptible, Benzyl Penicillin can be used, especially in early-stage cutaneous infections. Cephalosporins are generally contraindicated due to resistance.
• Antitoxins: Raxibacumab (monoclonal antibody) or anthrax immunoglobulin are used to neutralize anthrax toxins, particularly in severe or systemic cases.
• Drainage of pleural effusions and use of corticosteroids (e.g., IV dexamethasone) may be necessary in severe inhalational anthrax to reduce inflammation.
• Prophylaxis: Post-exposure prophylaxis with ciprofloxacin or doxycycline for 60 days is recommended for individuals exposed to anthrax spores (e.g., bioterrorism, laboratory exposure).

References

• Centers for Disease Control and Prevention Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults
• World Health Organization: Anthrax Overview
• Anthrax: MedlinePlus Medical Encyclopedia