BW Agents: Botulinum toxin

J.A. Sliman, MD, MPH

LCDR MC(FS) USN

Preventive Medicine Resident

Johns Hopkins Bloomberg

School of Public Health

Toxins

• Different from chemical weapons– Naturally occurring– Non-volatile– Non-persistent & no person-to-person spread

• Utility mostly limited by low toxicity– More effective as terrorist devices

Botulinum

• Produced by Clostridium botulinum– 7 related neurotoxins, types A through G

• Usually seen as a food-borne illness– Aerosol attack will produce similar symptoms

• Toxins are easily obtained from cultures and easily aerosolized

BW History

• Numerous cases of food-borne outbreak– Usually resulting from ingestion of improperly

canned foods

• Weaponized by FSU, researched extensively

• Weaponized by Iraq – Admitted in 1991, weapons found in 1995

BW/BT Significance

• Easy to produce & weaponize

• Can be aerosolized or placed into food

• Most toxic BW/BT agent by weight– LD50 = 0.001g/kg body weight– 15,000x more toxic than VX– 100,000x more toxic than Sarin

Mechanism

• Binds presynaptic nerve terminals at NMJ & at cholinergic autonomic sites

• Prevent release of acetylcholine– Opposite of organophosphate nerve agents

• Bulbar palsies & skeletal muscle weakness

Clinical botulism

• Symptoms start 24-36 hours after inhalation– Ingestion = shorter time of onset– Onset determined by dose

• Early bulbar signs followed by progressive, descending, symmetric skeletal muscle weakness & paralysis

Clinical botulism

• Culminates abruptly in respiratory failure– Can happen within 24 hours of onset

• Patients remain afebrile throughout

• CSF clear, no MSE changes– Distinguishes it clinically from meningitis

Diagnosis

• No antibody response (usually)

• Serum or gastric bioassay may be positive

• Usually a clinical diagnosis

• No cholinergic symptoms

Management

• CFR = 100% if not treated

• Ventilatory assistance cuts CFR to 5%

• Intensive nursing imperative

• Recovery may take months but is usually complete

Antitoxin

• Equine antitoxin highly effective– Useful against food-borne illness– Useful against aerosol attack as post-attack

prophylaxis prior to symptom onset

• Must do skin testing prior to use– Desensitization is effective if skin test is (+)

Vaccine

• Experimental, not FDA approved

• Available for use in case of suspected attack

• 0, 2, 12 weeks + booster every year

Botulinum toxin

• Bulbar signs + progressive, descending symmetric flaccid paralysis

• Afebrile, no anticholinergic or CSF signs

• Use antitoxin in case of attack