Botulism

Botulism

A young female IV drug abuser presented with dysarthria, diplopia and weakness with loss of her gag reflex. She had recently had an abscess wound on her arm debrided. She was intubated for airway protection, and underwent early tracheostomy. She was treated with intravenous antibiotics and botulism antitoxin after electromyography and nerve conduction studies were consistent with a diagnosis of botulism. She was weaned from the ventilator within 2 weeks and the Health Protection Agency later confirmed the presence of botulism neurotoxin A from wound swabs.

What are the clinical features of Botulism and how is it managed?

Helen Vollmer

Botulism is caused by botulism neurotoxin, produced by the bacterium Clostridium botulinum. It is commonly found in the soil and can survive for long periods as a spore. There are 3 main types of botulism; food-borne, intestinal (organism proliferates in the gut) and wound botulism. It can occur due to deliberate exposure (1). There were no reported cases of wound botulism in the UK before 2000 but the incidence has been increasing since then.(2) It is associated with subcutaneous and intramuscular injection of heroin (3).

C.botulinum is a gram positive, anaerobic bacterium that produces 7 neurotoxins. The Neurotoxins A, B and E cause most cases of human botulism, type A is commonest in wound botulism and is the most severe, with two-thirds of patients requiring ventilation (4). The neurotoxins bind irreversibly to presynaptic membranes of motor and autonomic cholinergic junctions preventing acetylcholine release. Clinical recovery correlates with formation of new presynaptic end plates (4).
Typical presentation is afebrile, descending symmetrical flaccid paralysis, which spares sensory nerves (2). Wounds may not be obviously infected.

Symptoms and signs(3)
Cranial nerves: Diplopia, blurred vision, photophobia, ptosis, dilated pupils, nystagmus, facial weakness, dysphagia, dysarthria, dysphonia
Peripheries: Weakness in the neck and arms followed by respiratory muscles and lower body, ataxia.
Autonomic system: 
 Bladder distension, urinary incontinence/retention, paralytic ileus, dry mouth, postural hypotension,
Gastrointestinal: Nausea, vomiting, diarrhoea, abdominal pain

The clinical course varies from a mild illness to respiratory failure, which may be fatal within 24 hours, before other symptoms and signs manifest. Differential diagnoses include Guillian-Barre syndrome and its Miller Fisher variant, organophosphate poisoning, and myasthenia gravis.

Diagnosis confirmation is by identifying C.botulinum neurotoxins in wound, faeces or serum samples by bioassay and neutralisation assays at the Food Safety Microbiology Laboratory. Electromyelography aids diagnosis; low amplitude compound muscle action potentials (CMAPs) in response to a supra-maximal stimulus are consistent with botulism. Incremental responses to tetanic stimulation suggests increases in acetylcholine release due to a pre-synaptic transmission defect (3).

Specific treatment includes wound debridement, trivalent anti-toxin (A, B and E), benzylpenicillin and metronidazole. Antitoxin may reduce mortality and length of , illness however the effects of benzylpencillin on the clinical course are questionable (4).
Antitoxin cannot reverse existent paralysis but prevents subsequent nerve damage by neutralising unbound toxin. A retrospective analysis of 134 cases showed a 10% mortality rate in patients receiving antitoxin within 24 hours of presentation, 15% mortality in cases receiving antitoxin after 24 hours and 46% in those who weren’t given antitoxin. Early deaths were due to failing to diagnose and deaths after two weeks were a result of long-term mechanical ventilation (6).
Patients should be regularly assessed for loss of gag and cough reflexes, vital capacity and inspiratory force. Supportive therapies include ventilation and management of autonomic dysfunction.

Another retrospective analysis of 20 patients in the 1990’s found that in the group given antitoxin within 12 hours of presentation 57% required mechanical ventilation versus 85% in the group that received antitoxin after 12 hours. Similarly the duration of ventilation was 35 days versus 54 days. The investigators found that early tracheostomy (within 10 days of intubation) was also associated with less ventilated days (45 versus 60) (8). Pneumonia is the commonest complication within 48 hours, presumably secondary to aspiration.

Magnesium-containing compounds and aminoglycosides should be avoided because of the risk of potentiating the toxin’s actions (5,6). Most cases fully recover but can take months. Reduced exercise tolerance and autonomic dysfunction has been found up to 2 years afterwards (4). In 5-10% of cases it is fatal, usually due to respiratory failure (1).


References:

1) http://www.hpa.org.uk/topics/infectiousdiseases/infectionsAZ/botulism
2) Wenham TN. Botulism: a rare complication of injecting drug use. Emergency Medicine Journal 2008; 25(1): 55-6
3) Brett MM, Hallas G, Mpamugo O. Wound botulism in the UK and Ireland. Journal of Medical Microbiology 2004; 53: 555-61
4) Mulleague L, Bonner SM, Samuel A et al. Wound botulism in drug addicts in the United Kingdom. Anaesthesia 2001; 56: 120-3
5) Mackle I, Halcomb E, Parr MJA. Severe adult botulism. Anaesthesia and Intensive Care 2001; 29: 297-300
6) O’Sullivan JM, McMahon G. Descending polyneuropathy in an intravenous drug user. European Journal of Emergency Medicine 2005; 12(5): 248-50
7) Royl G, Katchanov J, Stachulski F et al. Diagnostic pitfall: wound botulism in an intoxicated intravenous drug user presenting with respiratory failure. Intensive Care Medicine 2007; 33; 1301
8) Sandrock CE, Murin S. Clinical predictors of respiratory failure and long-term outcome in black-tar heroin-associated wound botulism. Chest 2001; 120(2): 562-6
9) Young D, Harrison DA, Cuthbertson BH, Rowan K et al. Effect of early v late tracheostomy placement on survival of patients receiving mechanical ventilation: the TracMan randomised trial. JAMA 2013; 309(20): 2121-9

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