Intestinal botulism

Botulism is a neuroparalytic, primarily foodborne illness first described in 1897 (GDC, 1998). The disease is caused by a toxin produced by the anaerobic bacterium Clostridium botulinum. Although botulism is rare, it can kill rapidly and foodborne botulism is a public health emergency carrying significant risk for widespread disease and death, as potentially preventable deaths may occur if the source of botulism is not discovered and eliminated. There are classically four major types of botulism foodborne botulism, infantile botulism, wound botulism, and intestinal botulism. 

Ingestion is the primary exposure pathway for botulism. Wound botulism occurs when the bacterium encounters devitalized human tissue, synthesizes toxin, and thus causes disease. Intestinal (adult and infant types) botulism involves ingestion of spores or the live bacterium and, due to impaired intrinsic defenses, the gastrointestinal tract becomes colonized with Clostridium botulinum. In infant type, the mucosal surface of the intestines is susceptible to colonization due to multiple factors including decreased acidity of the stomach and lack of bile of acids, which are natural barriers. In adult-type intestinal botulism, patients have had surgical vagotomy/... 

Botulism is a disease caused by ingestion of foods contaminated with Clostridium botulinum (food-borne botulism) or, very rarely, by wound infection (wound botulism) or colonization of the intestinal tract with Clostridium botulinum (infant botulism). The toxins block the release of acetylcholine. Botulism is characterized by generalized muscular weakness, which first affects eye and throat muscles and later extends to all skeletal muscles. Flaccid paralysis can lead to respiratory failure. 

Botulism is a potent neurotoxin produced from Clostridium botulinum that is an anaerobic, spore-forming bacterium. There are three different types ofbotulism Foodborne botulism occurs when a person ingests a pre-formed toxin that leads to illness within a few hours or days. Foodborne botulism is a public health emergency because the contaminated food may still be available. Infant botulism occurs in a small number of susceptible infants each year who harbor C. botulinum in their intestinal tract. Wound botulism occurs when wounds are infected with C. botulinum that secretes the toxin. Approximately 100 cases of the three types of botulism are reported within the United States each year about 5 percent are wound botulism, 25 percent are foodborne botulism, and a full 70 percent are infant botulism. Death can result from respiratory failure, but those who survive may have fatigue and shortness of breath for years. 

The role of C2 toxin in disease is not clear because all C. botulinum strains that produce C2 toxin also synthesize extremely potent neurotoxins, the effector molecules of botulism. When Simpson compared the pharmacological properties of C. botulinum neurotoxin type Cl with C2 toxin in detail, it became obvious that C2 toxin does not cause the flaccid paralysis symptoms attributed to classic botulism. However, isolated C2 toxin is a potent enterotoxin that proves lethal in various animals 2 pmol of C2 toxin readily kill mice, rats, guinea pigs, and chickens within 1 h after application. For mice, the LD50 (i.v.) of C2 toxin is less than 50 ftnol. Ohishi and Odagiri also reported that C2 toxin causes necrotic, hemorrhagic lesions in the intestinal wall, whereas Simpson reported that C2 toxin elicits hypotension as well as fluid accumulation in the lungs. ... 

Botulism also affects animals, where intoxication is caused by C. botulinum types C and D. A bovine disease visceral botulism was reported in Germany (Bohnel et al., 2001). It was caused by a long-lasting exposure to low quantities of botulin toxin that interfered with the neurological control of intestinal physiology. Visceral botulism in cows may pose a health risk for milk consumers, although to date there are no precise data on how serious the problem is (Cobb et al., 2002). 

All botulin neurotoxins act in a similar way. They only differ in the amino-acid sequence of some protein parts (Prabakaran et al., 2001). Botulism symptoms are provoked both by oral ingestion and parenteral injection. Botulin toxin is not inactivated by enzymes present in the gastrointestinal tracts. Foodborne BoNT penetrates the intestinal barrier, presumably due to transcytosis. It is then transported to neuromuscular junctions within the bloodstream and blocks the secretion of the neurotransmitter acetylcholine. This results in muscle limpness and palsy caused by selective hydrolysis of soluble A-ethylmalemide-sensitive factor activating (SNARE) proteins which participate in fusion of synaptic vesicles with presynaptic plasma membrane. SNARE proteins include vesicle-associated membrane protein (VAMP), synaptobrevin, syntaxin, and synaptosomal associated protein of 25 kDa (SNAP-25). Their degradation is responsible for neuromuscular palsy due to blocks in acetylcholine transmission from synaptic terminals. In humans, palsy caused by BoNT/A lasts four to six months. 

Botulism is most commonly caused by ingestion of a neurotoxin produced by Clostridium botulinum in improperly canned food. Poisoning may also occur after wound contamination with the organism. Infant botulism may occur when spores of the organism germinate and manufacture the toxin in the intestinal tract of infants. Botulinum toxin works by inhibiting ACh release at all cholinergic synapses. 

Heckly RJ, Hildebrand GJ, Lamanna C (1960) On the size of the toxic particle passing the intestinal barrier in botulism. J Exp Med 111 745-59... 

The data about fields of application of Silics in clinics for treatment for infectious diseases are presented in Table 4. From Table 4 it is evident that the field of application of Silics is rather large and covers both intestinal infections and toxicoses which victimize infants, as well as viral hepatitis, and botulism. It is appropriate to mention here that inclusion of Silics into the complex treatment of patients suffering from salmonellosis, dysentery, and intestinal toxicoses accelerates normalization of clinic manifestations of these diseases by a factor of two and more. In the case of botulism the normalization of symptoms characteristic of lesions of the nervous system is shortened by almost 4 days. If intestinal infections are not severe, Silics can be recommended as a single therapeutic agent. In the case of a considerable diarrheal syndrome it is more expedient to use it together with rehydration substances. Inclusion of Silics into a complex of therapeutic agents for patients suffering from viral hepatitis substantially accelerates recovery rates of patients, so that their normal level of bilirubin and activity of alanine aminotranspherase are recovered within shorter periods of time. 

Foodborne botulism accounts for approximately 1,000 cases per year worldwide, of which approximately 30 occur in the United States. Home processed foods account for 94% of U.S. cases. Infantile botulism, a form of the disease in which C. botulinum spores are ingested by infants due to food contamination, occurs in approximately 60 children per year in the United States, more than half of which are in California. Wound botulism, typically involving intravenous drug users who either inject drugs intravenously or in the subcutaneous tissue (a practice known as skin-popping ), is reported one to three times per year in the United States. It can also occur in other types of contaminated wounds such as a severe crush injury or other areas of contaminated avascular tissue. Botulism due to intestinal colonization by C. botulinum is extremely rare only seven cases have been reported in the literature (CDC, 1998). 

Type F toxin was only associated with two reported outbreaks of human foodbome botulism prior to 1998 (Maselli, 1998). The first of these outbreaks occurred in Denmark (on the Island of Langeland) and was attributed to a contaminated liver paste product (Muller and Scheibel, 1960 Richardson et al, 2004). The second outbreak, in 1966, affected three individuals in California and was associated with home-made venison jerky (Midura et al, 1972 Richardson et al, 2004). While a few other type F botulism cases have been reported, they are generally thought to have resulted from intestinal colonization and type F toxin production by another related species, C. baratii (Hall et al, 1985 Richardson et al, 2004). A recent report of a type F botulism case in California provided some additional insight into this uncommon toxin... 

Amon, S. (1995). Botulism as an intestinal toxemia. In Infections of the Gastrointestinal Tract (M. Blaser, P. Smith, J. Ravdin, H. Greenberg, R. Guerrant, eds), pp. 257-71. Raven Press, New York. 

Chia, J.K., Clark, J.B., Ryan, C.A., Pollack, M. (1986). Botulism in an adult associated with foodhome intestinal infection with Clostridium botulinum. N. Engl. J. Med. 315 239-41. 

McCroskey, L.M., Hatheway, C.L. (1988). Laboratory findings in four cases of adult botulism suggest colonization of the intestinal tract. J. Clin. Microbiol. 26 1052-4. 

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. 

Three classified types of botulism (foodborne, intestinal-infant type, and wound) result from infection... 

Natural human botnlism, a relatively rare disease, occurs in four epidemiologic forms food-borne, infantile, wound, and adult botulism from intestinal colonization (38). None of these is transmissible person to person. All four forms result from absorption of the toxin into the bloodstream through the mucosa, such as the gastrointestinal tract or a wonnd. The toxin cannot penetrate intact skin, hi the United States, fewer than 200 cases of human botuhsm occur each year (36). 

The least common form of human botulism, botulism from intestinal colonization, includes cases in patients greater than 1 year of age not associated with ingestion of contaminated food or wound infection with the only possibility being intestinal colonization (38). Stool in these patients will contain toxin and C. botulinum, and the suspected food may contain spores without preformed toxin. Some cases occur in patients with a history of gastrointestinal surgery or inflammatory bowel disease, conditions that could support enteric colonization of B. botulinum (38). In 2001, in the United States, one case of adult colonization botulism occurred in a 45 year old who survived (39). 

Under rare conditions, adults may manifest a syndrome similar to that of infant botulism. Such cases generally occur in hospitalized patients treated with a long course of multiple antibiotics that eliminate the normally suppressive intestinal flora other predisposing factors include inflammatory bowel disease and surgical alterations of the bowel (Fenicia et al., 1999). 

Amon, S.S. 1995. Botulism as an intestinal toxaemia. In Infections ofthe Gastrointestinal Tract, eds. M.J. Blaser, P.D. Smith, J.L Ravdin, H.B. Greenberg, and R.L. Guerrant, 257-271 New York, NY Raven Press. 

Fenicia, L., Franciosa, G., Pourshaban, M., and Aureli, P. 1999. Intestinal toxemia botulism in two young people, caused by Clostridium butyricum type E. Clin. Infect. Dis. 29 1381-1387. 

In adults, botulinum intoxication generally results from ingestion of preformed toxin elaborated in contaminated foods (foodbome), or from colonization by Clostridium botulinum of deep wounds with subsequent production of toxin (wound botulism). A third form, termed infant botulism, is observed in young infants and originates from colonization of the large intestine by Clostridium botulinum with subsequent production and absorption of toxin. Rarely, adults also exhibit a syndrome resembling infant botulism and some authors regard this as the fourth manifestation of botulism. ... 

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