Botulinum

The botulinum toxins are a group of seven related neurotoxins produced by the spore forming bacillus Clostridium botulinum and two other Clostridia species. These toxins, types A through G, are the most potent neurotoxins known. The spores are ubiquitous, they germinate into vegetative bacteria that produce toxins during anaerobic incubation. Industrial scale fermentation can produce large quantities of the toxin for use as a BW agent. Botulinum could be delivered by aerosol or used to contaminate food or water supplies. When inhaled, these toxins produce a clinical picture very similar to food borne intoxication, although the time to onset of paralytic symptoms after inhalation may actually be longer than for food borne cases, and may vary by type and dose of toxin. The clinical syndrome produced by these toxins is known as "botulism".

It is feasible to deliver botulinum toxins as an aerosolized biological weapon, and several countries and terrorist groups have weaponized them. Botulinum toxins were weaponized by the US in its old offensive BW program. Evidence obtained by the UN in 1995 revealed that Iraq had filled and deployed over 100 munitions with nearly 10,000 liters of botulinum toxin. The Aum Shinrikyo cult in Japan weaponized and attempted to disseminate botulinum toxin on multiple occasions in Tokyo prior to their 1995 Sarin attack in the Tokyo subway.

As the most poisonous substance known, crystalline botulinum toxin in the amount of a single gram, evenly dispersed and inhaled, would kill more than a million people. To give you an idea of its potency, botulism is 275 times more toxic than cyanide, and 100,000 times more toxic than sarin nerve gas. Botulism has already been weaponized, and sits ready for deployment around the world.

Clinical Presentation

Incubation period 24 to 36 hours for foodborne, 3 or more days for wound, and 72 hours in inhalation. Autonomic features are characteristic: Anticholinergic effects (dry mouth, ileus, constipation, urinary retention), mydriasis and nausea/vomiting secondary to functional obstruction. Descending paralysis is the prominent neurological feature and includes ptosis, diplopia, blurred vision, enlarged and sluggish pupils, dysarthria, dysphonia, and dysphagia. Respiratory failure may occur secondary to muscle weakness. Botulism does not cross the blood-brain barrier, sensorium remains intact.

Diagnosis is primarily a clinical one. Biowarfare attack should be suspected if multiple casualties simultaneously present with progressive descending flaccid paralysis. Lab confirmation can be obtained by bioassay of the patient's serum. Other helpful labs include: ELISA or ECL for antigen in environmental samples, PCR for bacterial DNA in environmental samples, or nerve conduction studies and electromyography.

Treatment

Trivalent antitoxin can be obtained from the CDC via state and local health departments. The antitoxin should be administered as soon as possible to neutralize the circulating toxin. In mass casualty setting, if neurological findings are present, do not delay antitoxin use for laboratory confirmation.

The dose for an individual with no known sensitivity is a single 10ml vial IV, diluted 1:10 in 0.9% saline solution. Treatment of botulism in patients with known sensitivity requires serial administration of diluted antitoxin/serum at 20 minute intervals as long as no adverse reactions occur.

Prophylaxis

A pentavalent toxoid of Clostridium botulinum toxin types A, B, C, D, and E is available as an IND for pre-exposure prophylaxis. The currently recommended primary series of 0, 2, and 12 weeks, followed by a 1 year booster induces protective antibody levels in greater than 90% of vaccines after one year. Adequate antibody levels are transiently induced after three injections, but decline prior to the one year booster.

Contraindications to the vaccine include sensitivities to alum, formaldehyde, and thimerosol, or hypersensitivity to a previous dose.