Chapter 33 Botulism
Botulism is a disease caused by one or more of the seven toxins, which may be produced by various strains of Clostridium botulinum, a spore-forming, obligate anaerobic bacillus, commonly found in the soil and very easily isolated.1 The clostridial neurotoxins are the most toxic substances known, and only tetanus toxin from C. tetani and Shigella neurotoxins appear to have potencies of the same order of magnitude.2,3
In the 1930s the Japanese biological warfare group (Unit 731) fed C. botulinum cultures to prisoners in Manchuria, and the United States’ biological weapons program, which was ended in 1970, produced botulism toxin and botulism toxoid in the 1940s in response to suspected German toxin weapons.2 Botulism is an acute, afebrile, symmetric, descending flaccid paralysis that always begins in the bulbar musculature in humans, but is a progressive, symmetric, ascending paralysis in dogs.4,5 Botulinum toxin remains a potential terrorist weapon delivered either by contaminating food or feed stuffs or in an aerosol form. The likelihood of botulinum toxin contaminating municipal water supplies is highly unlikely because the toxin is rapidly inactivated by standard potable water treatments, and large amounts of toxin would be required.4 There are some doubts whether botulinum toxin could be a weapon because of constraints in concentrating and stabilizing the toxin for aerosol dispersion.2 A deliberate release of a point-source aerosol botulinum toxin in an urban environment could incapacitate or kill approximately 10% of the exposed human population.2 At a minimum, the same percent morbidity and mortality could be expected of an exposed animal population.
SOURCES
The seven distinct botulinum toxins are defined by their antigenicity.2 In addition to C. botulinum, other clostridial strains may produce the toxins. The toxin is a dichain polypeptide weighing approximately 150 kD, which consists of a 100-kD “heavy” chain and a 50-kD “light” chain. Botulinum toxin in solution is colorless, odorless, and, as far as is known, tasteless. It is inactivated by heat (>85° C for 5 minutes).2 The seven types of botulinum toxin (A-G) do not necessarily cause diseases in all mammals. Types C and D normally occur in domestic animals and wildlife, and type G is a soil isolate from South America. Primates are susceptible to aerosol samples of all three.2 Types A, B, E, and F have been isolated in food poisoning cases in humans. Exposure to naturally occurring botulinum toxin may occur by consuming poorly preserved food in the case of humans and possibly small animals, dogs and cats ingesting carrion, spoiled meat and compost piles, and herbivorous animals ingesting decomposing animal carcasses.5–7
TOXIC DOSE
LD50s (IV and intraperitoneal [IP]) of the various botulinum toxins range from 0.1 to 40 ng/kg (1 ng = 0.000001 mg).8 The cattle IV median lethal dose is 0.388 ng/kg.7 It is estimated that the oral dose of botulinum toxin is 500 to 700 times greater than the parenteral dose and 77 to 100 times greater than the inhalational dose.2 The estimated human parenteral lethal dose is 1.3 to 2.4 ng/kg, and the parenteral minimum lethal dose in humans is estimated to be 1 ng/kg. The human inhalational lethal dose is approximately 0.01 μg/kg, and the oral lethal dose is 1 μg/kg.4 Most avian species are affected by botulinum toxin, including domesticated and wild fowl.9,10 Based on a limited number of birds, the American turkey vulture (Cathartes aura septentrionalis) appears to be resistant to the effects of botulinum toxin.2,4,10
TOXICOKINETICS
Botulinum toxins may be absorbed via any mucosal surface, but most commonly are absorbed through the gastrointestinal tract following oral exposure.2 In the case of inhalational exposure, botulinum toxins may be absorbed through the lungs as has been shown experimentally in primates and in humans following a laboratory mishap.11 The botulinum toxin weapon was developed for this purpose. Botulinum toxins may be absorbed through devitalized wounds containing anaerobic tissue. The toxins do not penetrate through intact skin. The botulinum toxins are distributed by the blood to the various tissue, but they do not penetrate the blood-brain barrier. The biotransformation mechanisms, distribution kinetics, and excretion of the botulinum toxins are unknown.2
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