866 CLOSTRIDIUM 



the toxin prior to injection of animals. Tetanus toxin is not absorbed from the 

 intact alimentary canal ; there is evidence that it is destroyed by the digestive 

 juices. It combines with and is neiitralized by specific antitoxin. There is 

 evidence, based on a lack of parallelism in the toxicity of culture filtrates of CI. tetani 

 for different species of laboratory animals, that there is more than one component 

 in tetanus toxin. These hypothetical components, however, appear to have 

 a similar antigenic specificity (Ipsen 1940-41, Smith, M. L., 1942-43). Petrie 

 (1942-43) found corresponding variations in the activity of antitoxins, and con- 

 cluded that crude tetanus toxin contained varying proportions of a " primary " 

 toxin molecule, and an antigenic variant of it. From somewhat similar experiences 

 Friedemann and Hollander (1943) postulated qualitative differences between 

 tetanus toxins from various sources. 



The toxin of CI. hotulinum resembles tetanus toxin in many respects, but is 

 more resistant to heat and to acids. Thus it requires for its destruction a 

 temperature of 80° C. for half an hour. Normal hydrochloric acid fails to destroy 

 it even in 24 hours, but normal soda destroys it rapidly. It is non-dialysable. 

 The potency of the toxin varies ; it has been possible to obtain filtrates with a 

 M.L.I), for a guinea-pig of 0-000001 ml., but this is exceptionally strong. It is 

 often said to be the only exotoxin that can be absorbed from the alimentary canal, 

 but the recent work on enterotoxsemic diseases of sheep (see Chapter 78) suggests 

 that the £-toxin of CI. welchii shares this property. 



The general properties of the toxins of CI. welchii, CI. septicum, and CI. oedema- 

 tiens may be considered together. They are all moderately thermolabile, being 

 destroyed by heating to 70° C. for 30 to 60 minutes. They are hkewise destroyed 

 by weak concentrations of acids. When toxic filtrates are injected into guinea- 

 pigs or mice they give rise to a gelatinous oedema and a varying amount of necrosis. 

 Weinberg and Combiesco (1930) state that welchii toxin lyses the red blood cor- 

 puscles, producing hsemoglobinuria, causes focal areas of necrosis in the kidney 

 and liver, and leads to an increase in blood pressure, which may in its turn be 

 responsible for haemorrhages in various parts of the body. 



Before discussing the toxins of CI. welchii in particular, we must refer briefly 

 to the four main varieties of the species, each associated with a different disease 

 (see Chapter 78) ; these are the classical CI. welchii of human gas gangrene, " CI. 

 cf^m," causing lamb dysentery, "CI. paludis," causing the sheep-disease " Struck," 

 and " CI. ovitoxicum," causing an infectious enterotoxsemia in sheep. The claim 

 of the last three to specific status has not yet been established. Each variety, 

 however, was shown by Wilsdon (1931, 1933) to produce toxic filtrates that could 

 be distinguished by their content of a number of toxic components. 



Glenny and his colleagues (1933) identified five separate toxic components in culture- 

 filtrates of Wilsdon's types, a, (i, y, d, and e. The existence of these components was 

 confirmed by a number of workers (Bosworth and Glover 1935, Borthwick 1935, Mason 

 1935, Weinberg and Guillaumie 1936, DaUing and Ross 1938, Duffett 1938, Stewart 1940, 

 Taylor and Stewart 1941). Of these five components, CI. welchii Type A was at first 

 thought to contain only a. Prigge (1936, 1937) and Ipsen and his colleagues (Ipsen 1939, 

 Ipsen et al. 1939a, b) found two components, a and C, and in one Type A strain, a third 

 component, which they designated rj (see also Nagler 1940). It is now clear that Prigge's 

 C toxin is equivalent to Glenny's a, and British workers (see Bailing and Stephenson 

 1942) have recently adopted a convention whereby Prigge's a and C are designated 6 and a 

 respectively. The t] toxin of Ipsen retains its original designation. There are, therefore, 

 seven toxic components to consider, a, j8, y, d, e, 6 and r]. Space forbids more than a 



