PATHOGENICITY 869 



of these five organisms associated witii gas gangrene give rise to specific antitoxins 

 on injection into suitable animals. 



CI. chauvosi under suitable conditions forms a weak toxin that is very heat- 

 labile, being destroyed in 5 minutes by exposure to a temperature of 52° C. Injected 

 intravenously into mice in a dose of 0-025-0-5 ml., it causes respiratory embarrass- 

 ment and death within a few minutes. It is also toxic to guinea-pigs, though not 

 rabbits, on intravenous inoculation. Subcutaneous inoculation into mice and 

 guinea-pigs is not fatal, but produces a local blood-stained oedema (Kerrin 1934). 



It is interestmg to note that all the diSerent groups of CI. tetani give rise to 

 identical toxins ; the antitoxin prepared against any one type will neutralize the 

 toxins of all types. With CI. hotulinum it is otherwise. Type A toxin is different 

 from Type B toxin. By agglutination Type A strains can be divided into 4, and 

 Type B into 3 groups (Starin and Dack 1923), but the divisions do not appear to 

 be clear-cut. Three further types have been described, C, D, and E, which appear 

 to differ in the type of toxin produced. 



Pathogenicity. — The pathogenicity of the anaerobes appears to depend almost 

 entirely on their toxin production. CI. tetani, for example, multiplies locally, and 

 does not invade the body. CI. botulinum is not even a parasite ; it is apparently 

 unable to grow in the tissues, and its pathogenic effects are determined by the 

 formation of toxin in food-substances prior to their ingestion. CI. oedematiens 

 remains almost confined to the site of inoculation. CI. welchii and CI. septicum 

 become generalized in the final stages of an infection, but they multiply only 

 locally before the death of the animal. Tetanus, botulism, and to a large extent 

 gas gangrene are intoxications. 



Pathogenicity of CI. botulinum for Laboratory Animals. 



Monkeys. — Van Ermengem (1897) fed a Macacus rhesus with 5 ml. of a preparation 

 of macerated ham, which was known to be toxic. Symptoms developed in 12 hours, and 

 consisted of restlessness, crying, coughing, and sneezing ; later there was a secretion of 

 viscid mucus in the nose and mouth, leading to transient suffocation ; the pupils were 

 dilated, reacting weakly to hght. The animal became motionless, its head drooped, its 

 eyes were fixed and half covered by the lids. Death occurred after 24 hours from the time 

 of feeding. At necropsy the stomach, the bases of the lungs, and the meninges were con- 

 gested, and petechial haemorrhages were noticed on the arachnoid and throughout the brain 

 and medulla. 



Cats. — ^The typical toxaemia may be reproduced in cats by feeding, but more certainly 

 by subcutaneous injection of cultures or of toxin. After a latent period of about 24 hours 

 the animal becomes quiet, loses its interest in external objects, and may refuse food. In 

 2 or 3 days the characteristic paralyses appear, giving a peculiar facies to the animal. Its 

 general aspect is stupid, the lids remain open, the eyes fixed in a glassy stare, the pupils 

 dilated and sluggish in their reaction to light. The animal sits in a dark corner, moves 

 little, and when disturbed takes a few uncoordinated steps across the cage and drops down 

 as if exhausted. Its head droops and its tongue protrudes. Thick, viscous secretion fills 

 the throat and nose, and causes severe paroxysmal attacks of suffocation relieved by a 

 hoarse croup-like cough. The mew takes on a dull tone, and is succeeded by complete 

 aphonia. For the first 2 or 3 days milk is accepted, but later owing to the dysphagia 

 or complete aphagia it is left untouched ; when delivered by a pipette into the mouth 

 it is not swallowed, but trickles down the trachea and causes choking. No urine or faeces 

 are voided. The animal remains susceptible to sensory impressions till the end, but is 

 unable to express its emotions in any way. Death occurs after a week or more, according 

 to the dose, and is apparently due as much to starvation as to the lethal effect of the 



