TYPHUS FEVER 847 



SECTION XIII. 1 THE VIRUS OF TYPHUS FEVER. 2 



The micro-organism which causes typhus fever in man should be classified, 

 according to Ch. Nicolle, Conor and Conseil, with the filtrable viruses. 



The infecting agent is probably an intra-cellular parasite of the white cells 

 of the blood. By animal experiment it has been shown that the blood is 

 infective from an early stage of the incubation period until convalescence is 

 well established. To obtain successful results with filtered blood the latter 

 should be allowed to clot spontaneously and the serum should be filtered 

 through the most porous type of Berkefeld bougie. 



The results obtained by Nicolle and his co-workers are not in accordance with 

 the observations of Anderson and Goldberger and of Ricketts and Wilder in America. 

 But as Nicolle points out the American bacteriologists used for inoculation a pro- 

 duct obtained by filtering the serum after defibrinating and then centrifuging the 

 blood and Nicolle and his colleagues, Conor and Conseil, have themselves found 

 that this product on inoculation into animals susceptible to infection with the virus 

 of typhus fever is followed neither by infection of, nor by the appearance of immunity 

 in, these animals. And not only so but they find further that the serum obtained 

 from blood which has been allowed to clot spontaneously though generally non- 

 infective after filtration is not invariably so. In the opinion of Nicolle, Conor and 

 Conseil the only hypothesis which will explain their experimental observations is 

 that under ordinary conditions the amount of the virus which passes the filter is 

 generally too small to produce infection or immunity in experimental animals. 



From the observations of Ricketts and Wilder it would appear that Mexican 

 fever (El Tabardillo) and typhus fever are due to one and the same micro- 

 organism. 



Experimental infection. Apes and monkeys. The chimpanzee and some of 

 the lower monkeys (Macacus sinicus, M. rhesus, M. cynomolgus, and M . 

 inuus) are susceptible to infection on inoculation with blood from human 

 cases of typhus fever. Chimpanzees are highly susceptible but the lower 

 monkeys less so ; moreover it would appear that some individuals of a species 

 e.g. M. rhesus are susceptible while others are insusceptible. 



In the case of the lower monkeys in order to ensure infection in susceptible animals 

 not less than 45 c.c. of blood should be inoculated and it is better to inoculate 

 intra-peritoneally than sub-cutaneously. 



The incubation period varies both with the species of monkey inoculated and 

 also with the amount of blood used for the experiment. In the chimpanzee the incu- 

 bation period is about 24 days but in the lower monkeys it is apparently shorter 

 (13-22 days). Following the incubation period the temperature rises (40 C. or 

 higher) for 8-10 days and then falls fairly rapidly to normal. During the febrile 

 stage an eruption generally appears on the face but an injection of the conjunctivas 

 may take the place of a rash. The animal is obviously unwell for the time being 

 but about a week after the fever has disappeared it is restored apparently com- 

 pletely to its normal health. 



Guinea-pigs. Guinea-pigs can also be infected with the virus of human 

 typhus fever. 



The blood (2-3 c.c.) should be inoculated into the peritoneal cavity. The incuba- 

 tion period varies from 13 weeks and the fever (40-41 C.) lasts from 4-9 days. 

 The blood is infective for monkeys during the whole of the febrile period. 



In some cases the inoculated guinea-pig may exhibit no rise of temperature but 

 the blood is nevertheless infective. 



Gavino and Girard have been able to pass the virus through a consecutive series 



1 This section has been added. 



2 Gr. rC0os smoke, mist, fog. The word was employed by Hippocrates to define a 

 confused state of the intellect with a tendency to stupor ; and in this sense it is aptly 

 applied to typhus fever with its slow celebration and drowsy stupor (A. W. Moore). 



