A frantic mother calls your office stating that her sister had just told her that feeding honey to children causes botulism. She had given a quarter teaspoon of a locally grown honey to her infant daughter three days earlier and was now in a panic. The mother states that the child appears normal and has shown no evidence of illness over the past three days, specifically no constipation, lethargy, or swallowing difficulty. You ask her to bring the child to your office where you examine her. The child appears healthy and in no respiratory distress. She is breathing normally and is not pooling secretions. The girl readily drinks a baby bottle of water without any difficulty. Her eyes are wide open with no proptosis, and her pupils are normal and react swiftly to a penlight. No cranial nerve findings or muscle hypotonia are present. You tell the mother that although botulism has been associated with honey in infants, none of the disease’s features of descending paralysis, or odynophagia, are present and reassure her that her child does not have the disease. The mother asks whether there is “a test” to prove it definitively and whether there is an antidote for botulism. What do you tell her?

Botulinum is the first of the eight biotoxins in this book to be discussed. It is the only biotoxin included among the Category A agents, largely because of the ubiquity of the bacteria that produce it, its toxicity, the relative ease of production and dissemination, as well as the precedence of its use in warfare. Botulism is a neurologic syndrome caused by a toxic proteolytic enzyme produced by the bacteria Clostridia botulinum. Botulism derives its name from the Latin word for sausage because contaminated sausage was the source for several of the earliest described outbreaks of the disease. C. botulinum is a spore-forming, obligate anaerobe found most commonly in soil. The neurotoxin produced by the bacterium is responsible for the clinical disease known as botulism. Botulinum toxin includes seven different proteins (identified as A through G) that are secreted by four distinct but closely related types of Clostridia bacteria.

Botulinum toxin (botulinum) is the most potent toxin in existence: If dispersed ideally, 1 g could kill over a million people. Botulinum is colorless, odorless, and said to be without taste. Botulism is a medical emergency since proper treatment must be implemented quickly, including antitoxin and life support systems, to prevent death. Botulinum toxin as a weapon of bioterrorism possesses several distinctive features compared to other Category A agents, the most obvious being that it is the product of the microbe and not the microbe itself that causes the disease.

There are three naturally occurring forms of botulism: foodborne, wound, and intestinal. An additional form, resulting from the weaponization of botulism, is inhalational. Historically, many of the deaths associated with botulism resulted from exposure to improperly prepared and canned foods. It has found medical application in treating such conditions as tetanus, blepharospasm, strabismus, and most recently in cosmetic surgery. Further, although not FDA approved for these purposes, botulinum has been used to treat migraines, chronic back pain, achalaisa, and other conditions.

Botulism’s potential as a biowarfare agent can be traced to WWII when it was fed to Chinese prisoners of war by their Japanese captors. The U.S. military feared its possible use by Germany and so vaccinated soldiers just prior to the D-Day invasion. In accordance with President Nixon’s directive, botulism research and development ended in 1972, although other countries, notably the USSR and Iraq, continued their research and development efforts throughout the 1970s and early 1980s.

Acts of terrorism involving botulinum have occurred, with three separate attacks in Japan, including one at a U.S. military base. Fortunately, none of the attempts were successful. Of note, the botulinum used in these attacks was made from clostridium cultures grown from local soil samples. Governments believed to presently possess or have begun production of botulinum included Iran, North Korea, and Syria.

As a bioweapon, botulinum is far more potent per equivalent weight than any synthesized toxins, and is considered one of the most toxic substances known to humanity. Through automated processes, large quantities of botulinum can be produced and introduced in an attack as an aerosol or through contamination of the food or water supplies. Given that sporadic botulism is a foodborne illness, deliberate contamination of food sources pose a likely threat. No naturally occurring waterborne illnesses have ever been reported with botulinum. Inhalation results in a similar presentation to foodborne infection albet with a faster onset. This is possibly because of its slower absorption through the intestinal mucosa. Fortunately, the toxin has limitations as a weapon because aerosolization affects its stability and it cannot withstand standard water treatment methods.

C. botulinum is found throughout the world in soil. It may contaminate improperly cooked or prepared foods, particularly honey and home-canned foods with low acid content. Although botulinum toxin is stable in water, it is rapidly inactivated by standard water treatments and contamination of drinking water supplies requires enormous quantities of the biotoxin. For these reasons, waterborne botulism is impractical and unlikely as a means of terrorism. Consumers of contaminated foods, rather than food preparers, have become ill in the sporadic nondeliberate outbreaks of botulism reported in the medical literature.

Natural outbreaks of botulism are uncommon but can be seen in agricultural areas. Based on patterns from natural occurrences, there are fewer than 200 cases (including all forms) each year in the United States with no obvious age or gender discrimination. Foodborne botulism results in roughly 9 cases per year and 2.5 cases per outbreak of disease. The largest foodborne outbreak was in 1977 at a restaurant in Michigan where 59 cases occurred. Three of the seven isomers of botulinum (A, B, and E) are the most commonly seen in humans. F rarely occurs in humans, whereas C and D are more common in non-humans, and G does not appear pathogenic.

All three naturally occurring forms of botulism toxin (foodborne, wound, and intestinal) result from Clostridium synthesis of botulinum either in vivo or prior to entering the bloodstream. Botulinum enters the body via absorption through the mucosal linings of the gastrointestinal or respiratory tracts, or from a contaminated wound site. Importantly, botulinum cannot enter the body through intact skin. A bioterrorist attack with botulinum would likely be from an aerosolized form, although it is possible that it could occur through contamination of food or water. Some protection is offered by simply covering one’s mouth with thick or folded cloths such as a handkerchief. Fortunately, sunlight denatures the toxin rendering it harmless within one to three hours of exposure, and the chlorine content of most municipal water supplies inactivates approximately 85% of botulinum toxin. Foodborne outbreaks, natural or deliberate, require foods that are uncooked or are poorly cooked. Natural infections tend to occur from contaminated vegetables—particularly those with a relatively high pH, such as beans, corn, carrots, and peppers. Life support systems and botulinum antitoxin have decreased the mortality rate to less than 5%.

Naturally occurring botulism or botulinum toxin is not contagious and therefore is not passed from person-to-person. Unfortunately, advances in genetic engineering pose a theoretical risk for contagion. Reports that the former Soviet Union experimented with splicing the Clostridium gene that codes for botulinum toxin into an infectious bacterial agent remain unconfirmed. However, if successful, this would effectively create an infectious form of botulinum toxin.

Botulinum toxin is a protease that binds to neuromuscular junctions outside the central nervous system. The biological effects of botulinum toxin are composed of two polypeptide chains. When the B subunit binds (irreversibly) to the pre-synaptic motor neuron, the toxin is endocytosed into the terminal end of the axon. Once inside, subunit A cleaves the proteins needed for neuronal vesicles to release the neurotransmitter acetylcholine (ACh) into the synaptic cleft. Without the binding of ACh to post-synaptic receptors the neuron cannot be activated and motor paralysis results. Botulinum toxin does cross the blood-brain barrier so that its effects are limited to peripheral and autonomic nerves outside the central nervous system.

All forms of botulism present with the same general signs and symptoms. Foodborne botulism begins with nausea, vomiting, cramping, or diarrhea, although this is believed to be the result of other clostridial metabolites rather than the toxin itself. This distinction is noteworthy because even if a bioterrorist attack involved contaminated food or water, only the neurological effects will be seen because purified toxin rather than bacteria will be used. All presentations of botulism regardless of exposure route will be neurological.

Onset of symptoms is seen between twelve and thirty-six hours after exposure depending on the extent and amount of exposure. In animal studies, higher doses have symptom onset well under twelve hours whereas low doses have shown delays as long as days. Although there can be extreme variation in the scope and timing of symptoms, all cases include cranial nerve (CN) paralysis because the toxin always affects bulbar musculature (see Table 18–2 for clinical features).