804 HEMOPHILUS 



suggesting that in these circumstances antitoxin had an anti-aggressive eflfect. Ospeck 

 and Roberts (1944) were able to protect mice and rabbits against live baciUi or toxin 

 by previously administered antitoxin. (For active immunization of laboratory animals 

 by H. pertussis and various fractions of the organism, see also Cruickshank and Freeman 

 1937, Miller and Silverberg 1939, Mishulow et al. 1939, Silverthorne 1940, Silverthorne 

 and Cameron 1942, Holm and Bunney 1942, Lapin 1942, Strean et al. 1941). 



H. injluenzce-suis plays an important part in swine influenza (see Chapter 74). 

 H. canis was isolated by Friedberger (1903) from 19 of 20 dogs suffering from a 

 suppurative inflammation of the prepuce, but he was unable to reproduce the 

 disease with it, and concluded that it was a harmless parasite of the preputial sac. 

 It has also been isolated from normal dogs by Krage (1910), Kristensen (1922), 

 Eivers (19226), and Kirchenbauer (1934). 



Experimental Infections. 



H. influenzce.—Attem'pts to produce an infection resembling influenza in man by experi- 

 ments on human volunteers or on the higher apes are considered in Chapter 74. 



As regards the usual laboratory animals, the injection of large doses of living culture 

 (the growth from I to 1 blood-agar slope suspended in saline) into the peritoneum of rabbits, 

 guinea-pigs, or mice, often results in death within 24-48 hours. At necropsy petechial 

 haemorrhages may be found, scattered over the peritoneum, and sometimes over the 

 pleura. The suprarenals may be congested or hsemorrhagic. The organisms can be 

 recovered from the peritoneal cavity, but not often from the heart's blood. The cause 

 of death seems to be a toxaemia, rather than an invasive infection (see PfeifiFer 1893, Delius 

 and Kolle 1897, Mcintosh 1922). Similar results may be obtained with filtrates of cultures 

 in liquid media, and these may produce death on intravenous injection into rabbits or 

 guinea-pigs, though relatively large doses (0-5-5 ml.) are usually required (see Parker 

 1919, Ferry and Houghton 1919, Wollstem 1919, Mcintosh 1922). There is no evidence 

 that these filtrates contain an exotoxin in the usually accepted sense. In view of Pittman's 

 observations and of her reports that her smooth strains are more virulent than the usual 

 rough strains, it is of interest to note that many observers have recorded wide variations 

 in virulence when a number of strains are tested by the intraperitoneal injection of living 

 cultures. Mcintosh (1922), for instance, found that only a smaU minority of recently 

 isolated strains proved to be of high virulence when tested in this way. It would seem also 

 that strains of H. infiuenzce isolated from cases of meningitis are usually far more virulent 

 for laboratory animals than strains isolated from the respiratory tract, and that some of 

 these meningeal strains have definite invasive powers (Cohen 1909, Henry 1912, WoUstein 

 1915). The incorporation of the intraperitoneal infecting dose in mucin — a technique 

 which has been successfully apphed to enhancing the virulence of meningococci (see 

 Chapter 23)— increases the virulence of H. infiuenzce ; small doses produce a fatal septi- 

 caemia m mice against which anti-influenzal horse serum is protective (Fothergill, Dingle 

 and Chandler 1937) (see also Silverthorne 1940). Certain strains of H. infiuenzce of human 

 origin give rise to a fatal infection after mtracerebral injection of about 2,000 organisms 

 into mice ; other strains, and strains of H. para-infiuenzce are non- virulent by this route 

 (de Torregrosa and Francis 1941). 



H. pertussis.- — The effect of the intraperitoneal injection of this organism into rabbits 

 or guinea-pigs is very similar to that of H. infiuenzce. Here again large doses are required 

 to produce death, and the infection seems to be toxaemic rather than invasive (Bordet and 

 Gengou 1907, 1909, WoUstein 1909). Leshe and Gardner ( 1931) carried out a careful series of 

 experiments in which they determined the relative toxicity of suspensions of strains of 

 H. pertussis, antigenicaUy in Phase I, II, III or IV, by intraperitoneal injections in guinea- 

 pigs. They found that the minimal lethal dose of strains in Phase III or IV (rough strains) 

 was twenty to thirty times greater than the minimal lethal dose of strains in Phase I or 

 II (smooth, or relatively smooth strains). 



