Inhalation botulism

Botulism. Clinical features include symmetric cranial neuropathies (i.e., drooping eyelids, weakened jaw clench, and difficulty swallowing or speaking), blurred vision or diplopia, symmetric descending weakness in a proximal to distal pattern, and respiratory dysfunction from respiratory muscle paralysis or upper airway obstruction without sensory deficits. Inhalational botulism would have a similar clinical presentation as food-borne botulism however, the gastrointestinal symptoms that accompany foodborne botulism may be absent. 

Inhalational botulism cannot be clinically differentiated from the 3 naturally occurring forms... 

Cases of botulism that appear in temporal or geographic groups should prompt rapid investigation into foodborne sources of illness as well as raise the possibility of bioterrorism in the form of inhalational botulism. Any suspected or confirmed case of botulism should prompt immediate contact with local and state health departments. 

The basie syndrome of BoNT intoxieation is similar for all naturally oeeurring forms, as well as for inhalation exposure and does not vary appreeiably among serotypes (Simpson, 1986 Habermann and Dreyer, 1986 Hatheway et al, 1984 Jankovie and Brin, 1997). Based upon documented laboratory evidenee, human BoNT intoxication is caused by exposure primarily to serotypes A, B, E, and to a much lesser extent to serotype F disease manifests mostly as a result of foodbome, infant, and wound botulism (Habermann and Dreyer, 1986 Simpson, 1986). BoNTs are also lethal from inhalation of aerosohzed toxin, although this form is not generally observed in nature. 

The onset of symptoms in botulism depends upon the amount of toxin ingested or inhaled and the related kinetics of absorption. Time to onset can range from as early as 2 h to as long as 8 days, although symptoms typically appear between 12 and 72 h after consumption of toxin-contaminated food (Lecour et ah, 1988 Amon et ah, 2001). In a review of 13 foodbome botulism outbreaks involving 50 patients from 1970 to 1984, the incubation period ranged from 10 h to 6 days (Lecour et al, 1988). 

The natural occurrence of human foodbome and infant botulism translates into a wealth of information on the clinical signs and symptoms of disease. This information can be compared to the array of physiological and pathological findings in various species of experimental animals after oral administration of BoNTs. The ability for inhaled BoNTs to produce illness has also been documented in... 

Holzer, V.E. (1962). Botulism from inhalation. Med. Klin. 57 1735-8. (Translation original document in German)... 

Worldwide, sporadic cases and hmited outbreaks of botulism can occur when food and food products are prepared or preserved by improper methods that do not destroy the spores of Clostridium botulinum and permit the formation of botulinum toxin. In industrially developed countries, the case fatality rate of food-borne botulism is 5-10%. Person-to-person transmission of botulism is not known. Botulinum toxin is the most poisonous substance known and poses a major bioweapon threat. In addition to the clinical forms of natural botulism (food-borne, wound, and intestinal), there is a fourth, man-made form of inhalational botulism that results from aerosolized botulinum toxin. 

Chemical Abstracts Service Registry Number CAS 93384-43-1. Botulinum toxins comprise a series of seven related protein neurotoxins that prevent fusion of synaptic vesicles with the presynaptic membrane and thus prevent release of acetylcholine. Exposure in a battlefield or terrorist setting would most likely be to inhaled aerosolized toxin. The clinical presentation is that of classical botulism, with descending skeletal muscle weakness (with an intact sensorium) progressing to respiratory paralysis. A toxoid vaccine is available for prophylaxis, and a pentavalent toxoid can be used following exposure its effectiveness wanes rapidly, however, after the end of the clinically asymptomatic latent period. Because treatment is supportive and intensive (involving long-term ventilatory support), the use of botulinum toxin has the potential to overwhelm medical resources especially at forward echelons of care. 

Botulinum toxin is on the A list of potential bioterrorist weapons because of its toxicity, its lethality, its ease of production, ease of transport, ease of use, and the need for prolonged, intensive care of affected victims (36). The colorless, odorless, and probably tasteless toxin is the most poisonous substance known (36). The most efficient route of exposure through a terrorist attack would be inhalational, causing a distribution of illness distinctly different from naturally occurring human botulism. One gram of crystalline toxin dispersed through an airborne route, could kill up to 1 million people, although technical limitations on dispersal could reduce the number of casualties (36). 

Since inhalation bomlism does not occur in nature, aU outbreaks must be considered as suspicious. Prudence would dictate that each should be treated as a criminal or terrorist attack, unless other causes are found (Arnon et al., 2001). From the limited human and animal data currently available, inhalation bomlism does not have a unique presentation rather, the signs and symptoms resemble those of other forms of botulism. The latent period is comparable with that of foodborne bomlism without the early G1 signs (Adler, 2006). 

Franz, D.R., Pitt, L.M., Clayton, M.A., Hanes, M.A., and Rose, K.J. 1993. Efficacy of prophylactic and therapeutic administration of antitoxin for inhalation botulism. In Botulinum and Tetanus Neuroloxoins and Biomedical Aspects, ed. B. Das Gupta, 473 76. New York, NY Plenum Press. 

It is is the third most toxic substance known after plutonium and botulism it is a protein toxin that is extracted from the castor bean (Ricinus communis). The USA Centers for Disease Control (CDC) considers 500 pg to be the lethal dose of ricin in humans if exposure is from injection or inhalation. Ricin is poisonous if inhaled, injected, or ingested, acting by the inhibition of protein synthesis. While there is no known antidote, the US military has developed a vaccine. 

Symptoms of inhalation botulism may begin as early as 24-36 hours, or as late as several days, following exposure. Initial symptoms include ptosis, generalized weakness, lassitude, and dizziness. Diminished salivation with extreme dryness of the mouth and throat may cause complaints of a sore throat. Urinary retention or ileus may also occur. Motor symptoms usually are present early in the... 

Infant botulism is a consequence of intoxication by BoNT following ingestion or inhalation of clostridial spores that colonize the large intestine young infants. 

Inhalational botulism, the syndrome most likely to be seen on the battlefield, is rare. One incident involving accidental exposure of humans to botulinum toxin occurred in a laboratory in Germany and was reported in 1962.31 After conducting a post-... 

SIGNS AND SYMPTOMS OF INHALATIONAL BOTULISM, IN ORDER OF ONSET... 

Period of communicability For inhalation anthrax, brucellosis, botulism, or tularemia ... 

---