Botulinum Toxin: Facts & Information
Botulinum toxin poses a major bioweapons threat because of its extreme potency and lethality; its ease of production, transport and misuse; and the potential need for prolonged intensive care in affected persons. Botulinum toxin is the single most poisonous substance known.
A number of states named by the U.S. State Department as "state sponsors of terrorism" have developed or are developing botulinum toxin as a biological weapon. Aum Shinrikyo tried but failed to use botulinum toxin as a biological weapon.
Botulinum toxin is derived from the genus of anaerobic bacteria named Clostridia. Seven antigenic types of botulinum toxin exist, designated from A through G. They can be identified based on antibody cross reactivity studies - i.e., anti-A toxin antibodies do not neutralize the B through G toxins.
Naturally occurring botulism is the disease that results from the absorption of botulinum toxin into the circulation from a mucosal surface (gut, lung) or a wound. It does not penetrate intact skin. The toxin irreversibly binds to peripheral cholinergic synapses, preventing the release of the neurotransmitter acetylcholine from the terminal end of motor neurons. This leads to muscle paralysis, and in severe cases, can lead to a need for mechanical respiration.
The incubation period for food-borne botulism can be from 2 hours to 8 days after ingestion, depending on the dose of the bacteria or the toxin. The average incubation period is 12-72 hours after ingestion. Patients with botulism typically present with difficulty speaking, seeing and/or swallowing. Prominent neurologic findings in all forms of botulism include ptsosis, diplopia, blurred vision, dysarthria and dysphagia. Patients typically are afebrile and do not have an altered level of consciousness. Patients may initially present with gastrointestinal distress, nausea, and vomiting preceding neurological symptoms. Symptoms are similar for all toxin types, but the severity of illness can vary widely, in part depending on the amount of toxin absorbed. Recovery from paralysis can take from weeks to months and requires the growth of new motor nerve endings. In the event botulism is suspected, the hospital epidemiologist and local and state health departments should be contacted immediately.
Natural cases of botulism are rare and typically result from food contamination. Many types of food have been associated in outbreaks in the past, with the common factor being that implicated food items were not heated or were incompletely heated. Heat > 85oC inactivates the toxin. The largest botulism outbreak in the U.S. in the past century occurred in 1977, when 59 people became ill from poorly preserved jalapeņo peppers.
No cases of waterborne botulism have ever been reported. This is likely due to the large amount of toxin needed, and the fact that the toxin is easily neutralized by common water treatment techniques.
A deliberate aerosol or food-borne release of botulinum toxin could be detected by several features including: a large number of acute cases presenting all at once; cases involving an uncommon toxin type (C, D, F, G, or non-aquatic food associated E); patients with a common geographic factor but without a common dietary exposure; and, multiple simultaneous outbreaks without a common source.
Diagnosis and testing are available at the CDC and some local and state laboratories. The standard test for the toxin is the mouse bioassay. Unfortunately, this assay is time consuming. Future development is focused on rapid diagnosis/detection. Polymerase Chain Reaction (PCR) assays that can detect the Clostridia spp. bacterial DNA toxin sequences are currently under development. Enzyme Linked ImmunoSorbent Assays (ELISAs) are being developed to detect functionally active toxins.
In the event that there is a clinical suspicion of botulinum toxin, treatment with antitoxin should not be delayed for microbiological testing. In the U.S., licensed botulinum antitoxin is available from the CDC via state and local health departments. An investigational heptavalent antitoxin is held by the U.S. Army. Optimal therapy for botulism requires early suspicion of the disease and prompt administration of antitoxin in conjunction with supportive care. Supportive care for patients with botulism may include mechanical ventilators in the intensive care unit, parenteral nutrition, and treatment of secondary infections.
An investigational botulinum toxoid is used to provide immunity for laboratory workers. It has been used to provide immunity against botulinum toxin over the past 30 years. However, supply of the toxoid is limited, and use of it would eliminate possible beneficial uses of toxoid for medical purposes. The toxoid induces immunity over several months and so would not be effective for rapid, post-exposure prophylaxis.
Existing technologies could produce large reserves of human antibody against the botulinum toxin. Administration of such a therapy could provide immunity of up to a month or greater and obviate the need for rationing the equine antitoxin. The development of such a human antibody reserve would require sufficient resources be dedicated to this problem.