Botulism of Clostridium Infections
Botulism is usually intoxication resulting from the ingestion of preformed botilinum toxin. C. botulinum is widely distributed in the soil and vegetation; hence the intestinal contents of mammals, birds, and fish. 8 types (A, B, C1, C2, D, E, F, G) have been recognised, each elaborating an immunologically distinct form of toxin. In the US, only types A (51%), B (21%), and E (12%) are significant causes of human botulism. The geographic distribution of cases is in keeping with the isolation of various toxin types from the regional soil samples. For convenience, C. botulinum can be divided into four groups be cultural characteristics. Toxin production in some strains depends on the presence of specific prophages.
Botulinum toxins are the most powerful biological toxins known. The spores of C. botulinum are relatively heat-resistant and pressure sterilisation is necessary to ensures their destruction. In contrast to the spores, botulinum toxin is relatively heat-labile, being completely inactivated at 100oC for 10 minutes.
Botulism results from the ingestion of uncooked foods in which contaminating spores have germinated and elaborated toxin. Food that is not visibly fermented or spoiled may still contain botulinum toxin. The toxin is not inactivated by gastric acid or proteolytic enzymes. The toxin acts on the neuromuscular junction where cholinergic blockade occurs, producing a life-threatening illness with cranial nerve impairment and symmetric weakness or paralysis. Symptoms begin 18 to 36 hours after ingestion with weakness, dizziness, constipation and dryness of the mouth and pharynx. Nausea and vomiting may be present. Neurological symptoms soon develop with blurring of vision, dilatation of pupils, inability to swallow, difficulty in speech, urinary retention, generalised skeletal weakness and respiratory paralysis. The fatality used to be extremely high but has declined to around 15% in the US.
Infrequently, ingested C. botilinum may colonise the gastrointestinal tract of infants where it elaborates toxin: more than 500 cases of infant botulism have been recorded since it was first described in 1976. Wound contamination with C. botulinum has been associated with noninvasive infection and in vivo toxin formation, producing clinical wound botulism. In these cases, characteristic neurological abnormalities occur but no food source is implicated. However, C. botulinum does not germinate readily in tissue and IVDA represent a high-risk group.
In cases of suspected botulism, mice should be injected intraperitoneally with the patient’s serum, and with stool extracts and implicated food. If toxin is present, the mice will succumb within 1 to 5 days. Because toxin is detected infrequently in infant botulism, the diagnosis is usually established by the demonstration of toxin from the stool. Samples of the suspected food should also be cultured anaerobically with heat or alcohol treatment to select for spores.
Botulinum toxins are inactivated by their antitoxins. Treatment must be given early before laboratory results because once the toxin has been fixed and neurological symptoms have occurred, the antitoxin is not effective. Equine antitoxin is given IV, containing A, B, and E antitoxin. Most infants with botulism do not have toxin in their serum and are no longer acutely ill when the illness is diagnosed. Therefore antitoxin is rarely administered. Enaemas, carthartics, and gastric lavage are employed to facilitate the elimination of unabsorbed toxin provided paralysis is not present. Other individuals known to have ingested the same food as the patient should also be treated even if they are asymptomatic.
Tetanus arises from a neurotoxin produced by when spores of C. tetani germinate after gaining access to the wounds. The disease may develop after penetrating trauma, chronic skin ulcers, infections about the umbilical stump of newborn (neonatal tetanus), obstetric procedures (postabortal tetanus), and infected injection sites in IVDA. Unlike botulism, only one antigenic type of toxin is involved and therefore an effective montypic toxoid is available. C. tetani is a strict anaerobe without a capsule. Its spherical terminal spores give a characteristic “drumstick” appearance. It is found in the soil and faeces of farm and domestic animals. In humans, the faecal carrier rate is low (0-25%) suggesting that the organism’s presence is transient.
Most cases arises from small puncture wounds or lacerations. The infection remains localised to the site of entry. Access of tetanus spores to open wounds does not necessarily result in disease, especially in clean wounds where the oxygen supply is good and germination is inhibited. In necrotic or infected wounds, anaerobic conditions will permit germination. The incubation period ranges from several days to many weeks. The usual form of the disease is characterised by sever painful spasms and rigidity of voluntary muscles. Spasms of the pharyngeal muscles causes dysphagia and death may result from paralysis of respiratory muscles.
The diagnosis of tetanus is usually based on clinical findings alone. However, attempts should be made to culture C. tetani from all suspicious lesions. The organism can only be cultured from infective focus in 30% of cases. Antitoxin should be promptly administered in all cases of suspected tetanus. It is ineffective when the toxin is already fixed in the CNS. Tetanus immune globulin (TIG) prepared from persons who have been hyperimmunised with tetanus toxoid has supplanted conventional equine antitoxin. Careful debridement of the lesion and removal of foreign bodies should be carried out after TIG had been given. Penicillin should also be administered to prevent the germination of spores and further bacterial multiplication. Intensive supportive measures should be given.
Because spores of C. tetani are so widely distributed, the only effective way to control tetanus is by prophylactic immunisation. Tetanus toxoid is usually given as part of DPT. Whenever a previously immunised individual sustains a potentially dangerous wound, a booster dose of toxoid should be given. Non-immunised individuals should be given TIG.
A variety of species of clostridium are associated with invasive infection in humans i.e. C. perfringens, novyi, septicum, histolyticum, tertium, bifermentans, sporogenes. They are not highly pathogenic when introduced into healthy tissues; but in the presence of tissue injury, in particular damaged muscle, they can cause a rapidly progressive devastating infection characterised by the accumulation of gas and the extensive destruction of muscle and connective tissue. Pathogenesis is due to the production of various toxins with necrotising, haemolytic or other destructive properties.
There are three types of clostridial wound infection: wound contamination, anaerobic cellulitis, and true myonecrosis (gas gangrene). 80 to 90% of isolations of C. perfringens from hospital represent wound contamination which does not herald invasive infection. Anaerobic cellutitis is a clostridial infection that does not involve the muscle and is much less aggressive than gas gangrene. Germination occurs in damaged tissue where damage to the blood supply has reduced the supply of oxygen. The vegetative bacilli multiply and anaerobic cellulitis develops after several days. The marked gas formation is detectable by the resulting crepitus. Gas gangrene is an intensively aggressive highly lethal infection, primary of muscle. After the germination of clostridial spores in the injured muscle, bacterial multiplication and toxin production occur. A self-perpetuating cycle of progressive tissue injury ensue. The onset of the disease is sudden, usually following an onset of 6 to 72 hours after injury or abdominal surgery. Of the six clostridial species capable of producing gas gangrene, C. perfringens account for the majority of cases.
C. perfringens is present in the genital tract of 5% of women. After septic abortion, it may invade the uterine wall, producing extensive necrosis, high fever, and shock. Severe bacteraemia characteristically occurs. Bacteraemia caused by C. perfringens or other species occasionally occur in other debilitated patients e.g. leukaemia, other cancers, GI bleeding etc. Bacteraemia occur in 15% of patients with gas gangrene.
C. difficile had been found in 25% of cases of moderate diarrhoea resulting from treatment with antibiotics, especially clindamycin, ampicilllin, or cephalosporins. In the more severe reaction known as pseudomembranous collitis, C. difficile is found in 95% of cases. This occasionally fatal illness is characterised by diarrhoea, multiple small colonic plaques, and toxic megacolon. The antibiotic selects for overgrowth of organsism that produce a heat-labile toxin; faecal extracts from these patients are cytotoxic in cell culture. The enterotoxicity of C. difficile is due to two toxins; toxin A, and toxin B.
C. perfringens is a common organism frequently found in excreta from humans and animals and in raw meats, poultry and other foods, including dehydrated products. It can survive heat and dehydration by means of spores that remain dormant in food, soil, and dust. Illness occurs after eating food contaminated with large numbers of C. Perfringens grown from spores: the spores had been activated by heat shock. The enterotoxin is only produced during sporalation and not during vegetative growth. Multiplication of bacteria take place during long slow cooking and warm storage of food in the kitchen or canteen. Cooked meat, poultry, fish, stews, pies, and gravies are excellent media for growth at temperatures up to 50oC. There is little growth below 15oC. The spores of some strains of C. Perfringens can withstand long hours of boiling. The organism may be isolated in large numbers from boiled, stewed, steamed, braised, or even roasted foods, particularly those cooked in bulk and stored unrefrigerated for a few hours.
Symptoms occur 8 to 22 hours after consumption of the contaminated food. They include abdominal pain, profuse diarrhoea, and nausea, but rarely vomiting. Symptoms may continue for 12 to 48 hours. The symptoms occur as a result of an enterotoxin produced by a large number of ingested organisms. An effective amount of toxin is not usually formed in the food before it is eaten. There are 5 types of C. Perfringens (A to E) classified according to the various toxins they produce. Only two of these produce the enterotoxin which cause gastroenteritis: type A is the more common agent of food poisoning whereas type C is responsible for a more serious but rare condition known as enteritis necroticans.