Lec. No. 10 Dr. Manahil Clostridium botulinum (neurotoxic clostridia)
C. botulinum is the etiological agent of botulism, a food poisoning disease. Anaerobic, gram positive rods, spore forming. The spores present in soil that contaminate vegetable, meat, and fish. Spores resist boiling for 3-5 hrs. In canned food, and preserved food at home without adequate sterilization, the contaminated spores survive and can germinate, then vegetative cells produce toxin.
ToxinDuring the growth of C. botulinum and during autolysis of the bacteria, toxin is liberated into the environment.Toxin is heat labile, inactivated by boiling for several minutes, so the disease can be prevented by sufficient cooking.Seven antigenic verities of toxin (A-G) are known. Type A,B and E are the principle cause of human illness.Type A and B have been associated with a variety of foods and type E mostly with fish products.Botulinum toxin is the most powerful natural toxin.The lethal dose for a human is probably about 1-2g/kg.
Pathogenesis and clinical findings mostly the illness is not an infection. It is an intoxication resulting from the ingestion of food in which the organism has grown and produced toxin. Botulinum toxin is a neurotoxin. The toxin is absorbed from the gut and carried by the blood to the peripheral nerve synapses where it blocks the release of acetylcholine. The disease is a type of food poisoning that affects the motor and autonomic nervous systems. After an incubation period of 72hrs, there is descending weakness and flaccid paralysis with diplopia, dysphagia vomiting and respiratory muscle failure. There are no abdominal pain, diarrhoea or fever.
Toxicoinfectious BotulismThis type of disease describes the condition where viable bacteria enter the body, either through a wound or into the gut.The organisms grow and produce toxin locally if the conditions are appropriate.The toxin is absorbed and produce systemic effects similar to food –borne botulism.
Infant botulism In infant botulism, honey is the most frequent vehicle of infection. The infant ingests the spores of C. botulinum, and the spores germinate within the intestinal tract. The vegetative cells produce toxin as they multiply, the neurotoxin then absorbed into the blood stream. The toxin acts by blocking release of acetylcholine at synapses and neuromuscular junctions. Flaccid paralysis result. Wound botulism Wound botulism develops from toxin production by C. botulinum in contaminated wounds.
Laboratory diagnosis The toxin can be demonstrated in contaminated food and occasionally in the patient's serum. The clinical diagnosis of botulism is confirmed if the organism is isolated or toxin activity is demonstrated. Culture of the organisms from the feces and from the implicated food if it is available. Treatment Trivalent antitoxin (types A,B and E) must be given intravenously with respiratory support (mechanical respiration). These measures reduced the mortality to less than 25%.
Clostridium tetani
Is a large, motile, spore forming rod. The organisms produces round, terminal spores that give the appearance of drumstick.C. tetani is difficult to grown. The organism is proteolytic but unable to ferment carbohydrate. The spores found in soil, dust, hospital environment and faces of animals and man. The portal of entry is usually the wounds. Motile, non-capsulated, and obligate anaerobic. The flagellar antigens (antigenic structure) are 10 types.
Pathogenesis C.tetani is not an invasive organism. The infection remains strictly localized in the area of devitalized tissue into which the spores have been introduced. The disease is entirely a toxemia. Germination of the spores and development of vegetative organisms that produce toxin are aided by a-Necrotic tissue. b-Calcium salts. c-Associated pyogenic infections.
C. tetani produce two toxins: 1. tetanolysin an oxygen-liable hemolysin. 2. tetanospamin a heat liable neurotoxin, it is a polypeptide which can be split into 2 fragments A and B. The usual predisposing factor for tetanus is an area of very low oxidation-reduction potential. The tetanus toxin (neurotoxin), after its production at wound site reaches the CNS along the motor nerve trunks or via blood stream then it binds to ganglioside receptors and blocks the release of inhibitory mediators at spinal synapses results in hyperfexia and muscle spasm which may be generalized. Tetanospasmin is responsible for the clinical manifestation of tetanus.
Clinical diseases The disease (tetanus) is characterized by tonic contraction of voluntary muscles. Muscular spasms often involve first the area of injury and infection and then the muscles of the jaw (trismus, lock jaw) which contract so that the mouth can not be opened.
Other voluntary muscles became involved, resulting in tonic spasms.
The patient is fully conscious, pain may be intense. Death is due to respiratory failure. Tetanus, either generalized (the most common form) or localized in which the disease remains at the site of primary infection.A variant is cephalic tetanus, in which the primary site of infection is the head.
Neonatal tetanus (tetanus neonatorum) is associated with an initial infection of the umbilical stump that progress to become generalized. Neonatal tetanus result from: failure to protects the mothers by antitoxin immunization. lack of hygiene during and after delivery. Neonatal tetanus a disease in developing countries. The mortality in infants exceeds 90%.
Laboratory diagnosis The diagnosis based on the clinical picture and a history of injury. No microbiological or serological diagnosis. Culture results are positive in only about 30% of patients with tetanus.
Prevention and control Vaccination with tetanus toxoid. Wound care and metronidazole or penicillin therapy eliminate the vegetative bacteria that produce toxin. Prophylactic use of antitoxin (tetanus immunoglobulin). Surgical measures (wound debridement). Control associated pyogenic infection. Health education. Person to person transmission dose not occur. Recovered patients should receive a full course of immunization.
TreatmentPatients who develop symptoms of tetanus should receive muscle relaxants and assisted ventilation.Sometime they are given large doses of anti toxin (human tetanus immunoglobulin – HTIG) intravenously that derived from blood of volunteers hyperimmunized with toxoid.Penicillin or metronidazole.Good feeding.