BOTULISM

JAMA published a consensus article covering botulism as a biological weapon. The pdf file is available here:

Botulinum toxin is odorless and colorless. The largest outbreak of foodborne botulism occurred in Michigan in 1977 when 59 cases resulted from eating home-preserved peppers.

Botulinum toxin has been used as a terrorist weapon. The Aum Shinrikyo cult dispersed botulinum toxin in Tokyo and at US military bases in Japan between 1990 and 1995. In WWII, the US produced over a million doses of botulinum toxoid vaccine because of fears that Germany had prepared weaponized botulinum toxin. Iraq admitted producing over 19,000 liters of concentrated botulinum toxin to the UN inspection team. The US estimates that a point source release of botulinum toxin would incapacitate or kill 10% of the people within 0.5km.

Toxin is carried to the cholinergic synapses and blocks ACH release. All forms of botulism display the same neurologic signs. Food borne botulism can begin as soon as 2 hours after ingestion but can present 12-72 hours after ingestion. In experiments in monkeys, aerosol exposure produced symptoms 12-80 hours after exposure to 4-7 multiples of the LD50.

There are 3 forms of naturally occurring botulism: foodborne, wound, and intestinal. Aerosol or inhalational botulism is a weapon.

Normal neuromuscular junctions function are associated with release of acetylcholine (ACH) mediated by the assembly of a synaptic fusion complex. The fusion complex allows the synaptic vesicle containing the ACH to bind with the neuronal cell membrane resulting in release of the ACH (1).

In botulism, the toxin binds to the neuronal cell membrane (2-3) at the nerve terminus and enters the neuron. The toxin prevents the formation of the fusion complex (4) so that ACH cannot be released. Without ACH release, the muscle cannot function. The effect of the toxin is permanent (5) and is reversed by growth of new axonal terminals at the neuromuscular junction (takes weeks to months) (6).