Anthrax

Anthrax is an acute infection caused by Bacillus anthracis, a spore forming Gram positive bacterium. It occurs naturally through contact with infected animals or animal products (cutaneous and gastrointestinal disease) or through inhalation of spores (inhalational disease).

Inhalational disease carries the highest mortality and is a recognised agent of bioterrorism. It needs prompt recognition and immediate treatment, because clinical deterioration can be rapid.

Pathophysiology

Bacillus anthracis spores are highly resistant environmental structures. They germinate at the site of entry (skin, gastrointestinal tract or lungs).

The resulting vegetative bacteria produce a tripartite exotoxin (protective antigen, lethal factor and oedema factor). The toxin causes the characteristic local tissue necrosis and oedema. In systemic disease it causes the severe toxaemia and shock of advanced infection.

• Cutaneous anthrax is the commonest naturally occurring form. It presents as a painless, pruritic papule at the site of inoculation. Over several days it becomes a vesicular lesion and then a black, depressed, necrotic eschar (the pathognomonic finding), surrounded by significant non pitting oedema. It is generally not painful despite the striking local appearance.

• Inhalational anthrax starts with a non specific, influenza like prodrome (fever, malaise, myalgia, non productive cough) over one to several days. Abrupt deterioration follows, with high fever, severe respiratory distress, and mediastinal widening on chest imaging from haemorrhagic mediastinal lymphadenitis. It progresses rapidly to septic shock and death if untreated. Historically mortality was near universal without early treatment.

• Gastrointestinal anthrax follows ingestion of contaminated meat. It presents with severe abdominal pain, haematemesis, bloody diarrhoea and systemic toxicity. Mortality is high, because early recognition is often difficult.

Diagnosis is confirmed by culture of the organism from the relevant clinical specimen (skin lesion, blood, pleural fluid, cerebrospinal fluid). Gram stain shows characteristic large, box car shaped Gram positive bacilli. Polymerase chain reaction testing allows rapid confirmation, which is particularly important where bioterrorism related exposure is suspected.

In suspected inhalational disease, chest radiography or computed tomography characteristically shows a widened mediastinum with haemorrhagic lymphadenitis and, frequently, pleural effusion. Typical bronchopneumonic infiltrates are absent, which is an important distinguishing feature.

Any suspected case, particularly inhalational disease without a clear natural exposure history, requires immediate notification to public health and, where relevant, law enforcement authorities, because of the bioterrorism implications.

Systemic anthrax (inhalational, gastrointestinal, or cutaneous with systemic signs, or cutaneous lesions of the head and neck) requires combination intravenous antimicrobial therapy:

• ciprofloxacin 400 mg intravenously every 8 hours (or levofloxacin 750 mg intravenously once daily) as the backbone agent
• plus a protein synthesis inhibitor such as linezolid 600 mg intravenously every 12 hours or clindamycin 900 mg intravenously every 8 hours, given to suppress ongoing toxin production
• typically a third agent for the most severe presentations

Adjust to at least two active agents once susceptibility results are available.

Uncomplicated cutaneous anthrax without systemic involvement may be treated with oral monotherapy: ciprofloxacin 500 mg twice daily or doxycycline 100 mg twice daily. Give it for 7 to 10 days in naturally acquired disease. Extend to 60 days if bioterrorism related spore exposure is suspected, because of the risk of concurrent inhalational exposure and delayed germination of residual spores.

Anthrax antitoxin (raxibacumab or obiltoxaximab, monoclonal antibodies targeting protective antigen) is added to antimicrobial therapy for systemic disease. It neutralises circulating toxin and benefits patients independently of antimicrobial activity against the organism. This is valuable because antibiotics alone do not address toxin already produced and circulating.

Total duration of antimicrobial therapy for systemic disease is 14 days or longer depending on clinical response. Where inhalational spore exposure is possible, extend to a total of 60 days (combining intravenous and subsequent oral therapy), because residual spores germinate over a prolonged and unpredictable period.

Post exposure prophylaxis after confirmed or high risk inhalational spore exposure is ciprofloxacin 500 mg twice daily or doxycycline 100 mg twice daily for 60 days. Anthrax vaccine (where available) is considered as an adjunct for occupational or bioterrorism related exposure, under public health guidance.

Supportive care is essential given the severity of systemic disease. It includes aggressive management of septic shock, drainage of any significant pleural effusion, and intensive care support for respiratory or multiorgan failure. Notify public health promptly and investigate the source of exposure.