Clostridium Perfringens Toxins
|Common Name(s)||Clostridium Perfringens Toxin; Epsilon Toxin|
|Scientific Name(s)||Clostridium perfringens|
|Physical Attributes||Anaerobic, Gram-positive, sporeforming rod (bacilli)|
|Mode(s) of Transmission||Ingestion of bacteria or through open wound infection; three types: gas gangrene or clostridial myonecrosis (wound infection); enteritis necroticans or pig-bel (Type C); and clostridium food poisoning (Type A)|
|Likely BW Form(s)||Saboteurs or aerosol|
|Vector/Dormant Form||None; spores in food, soil, water, dust|
|Incubation Period||6-24 hours|
|Fatality||Rare in naturally occurring cases|
|Treatment||Antibiotics; antitoxins; surgical debridement; hyperbaric oxygen|
Clostridium perfringens is a common anaerobic bacterium associated with three distinct disease syndromes; gas gangrene or clostridial myonecrosis; enteritis necroticans (pig-bel); and clostridium food poisoning. Clostridium bacteria produce many different toxins, four of which (alpha, beta, epsilon, iota) can cause potentially fatal syndromes. In addition, they cause tissue death (necrosis), destruction of blood (hemolysis), local decrease in circulation (vasoconstriction), and leaking of the blood vessels (increased vascular permeability).
Gas gangrene is rare, with only 1,000-3,000 cases yearly in the U.S. Gas gangrene generally occurs at the site of trauma or a recent surgical wound. About a third of cases occur spontaneously. Patients who develop this disease spontaneously often have underlying blood vessel disease (atherosclerosis or hardening of the arteries), diabetes, or colon cancer. The onset of gas gangrene is sudden and dramatic. Inflammation begins at the site of infection as a pale-to-brownish-red and extremely painful tissue swelling. Gas may be felt in the tissue as a crackly sensation when the swollen area is pressed with the fingers. The edges of the infected area expand so rapidly that changes are visible over a few minutes. The involved tissue is completely destroyed.
Enterocolitis necroticans or pigbel is a rare condition characteristically affecting chronically malnourished people who abruptly increase their intake of protein. The classic presentation of the disease as seen in the highlands of Papua New Guinea is that of a necrotising enterocolitis after the ritual ingestion of contaminated pork. Symptoms include dehydration, weakness, diarrhea, necrosis of the interestines, and septicemia.
Perfringens poisoning is one of the most commonly reported foodborne illnesses in the U.S. There were 1,162 cases in 1981, in 28 separate outbreaks. At least 10-20 outbreaks have been reported annually in the U.S. for the past 2 decades. Typically, dozens or even hundreds of person are affected. It is probable that many outbreaks go unreported because the implicated foods or patient feces are not tested routinely for C. perfringens or its toxin. CDC estimates that about 10,000 actual cases occur annually in the U.S.
Each of these syndromes has very specific requirements for delivering inocula of C. perfringens to specific sites to induce disease, and it is difficult to imagine a general scenario in which the spores or vegetative organisms could be used as a biological warfare agent. There are, however, at least 12 protein toxins elaborated, and one or more of these could be produced, concentrated, and used as a weapon. Waterborne disease is conceivable, but unlikely. The alpha toxin would be lethal by aerosol. This is a well characterized, highly toxic phospholipase C. Other toxins from the organism might be co-weaponized and enhance effectiveness. For example, the epsilon toxin is neurotoxic in laboratory animals.
Gas gangrene is a well-recognized, life-threatening emergency. Symptoms of the disease may be subtle before fulminant toxemia develops, and the diagnosis is often made at postmortem examination. The bacteria produce toxins that create the high mortality from clostridial myonecrosis, and which produce the characteristic intense pain out of proportion to the wound. Within hours signs of systemic toxicity appear, including confusion, tachycardia, and sweating. Most Clostridia species produce large amounts of CO2 and hydrogen that cause intense swelling, hence the term "gas" gangrene, resulting in gas in the soft tissues and the emission of foul-smelling gas from the wound. Clinical features include necrosis, dark red serous fluid, and numerous gas filled vesicles. The infection may progress upto 10 cm per hour, and early diagnosis and therapy are essential to prevent rapid progression to toxemia and death. Pulmonary findings might lead to confusion with staphylococcal enterotoxin B (SEB) initially. Liver damage, hemolytic anemia, and thrombocytopenia are not associated with SEB and the pulmonary findings should be reversible in SEB.
No specific treatment is available for C. pefringens intoxication. Early antibiotic treatment is effective, if undertaken before significant amounts of toxins have accumulated in the body. If not treated the bacteria enter the bloodstream causing fatal systemic illness. The organism itself is sensitive to penicillin, and consequently, this is the current drug of choice. Recent data indicate that clindamycin or rifampin may suppress toxin production and provide superior results in animal models. Prompt surgical debridement and broad spectrum, intravenous antibiotics are the mainstay of therapy. Hyperbaric oxygen has not been proven effective in prolonging survival.
There is no available prophylaxis against most C. perfringens toxins. Toxoids are being used to prevent enteritis necroticans in humans, and veterinary toxoids are in wide use.
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