240 



F. FENNER AND J. CAIRNS 



low temperature (Sulkin, 1945; Briody et al., 1953) or by combining the 

 virus inoculum with various nonspecific irritants (Jones, 1950). 



C. Systems Involving Sequence 



We have discussed variation and virulence in those systems where either 

 one type of cell or one tissue is being infected. There remain those situations 

 where a definite sequence of tissues is infected as the virus progresses toward 

 that final stage by which it is regarded as virulent or not. 



skin: 

 invasion 

 multiplication 



regional lymph node 

 multiplication 



bloodstream : 

 primary viremia 



spleen & liver 

 multiplication 



bloodstream: 

 secondary viremia/ 



skin ■ U 



focal multiplication I ( 



antibody in 

 serum 



contamination 



of 

 environment " severe rasn 

 ulceration 



MOUSEPOX 



^ small intestine; 

 \fa?~\ invasion 

 ¥\%? multiplication 



I* 



v) mesenteric lymph nodes; 



fn i multiplication 



Y bloodstream-. 



primary viremia 



central focus of 

 multiplication 



bloodstream : 

 (secondary) viremia 



central nervous 

 system: 

 invasion ?via ganqta 

 multiplication 

 intra neural 

 spread 



antibody in 

 serum 



paralysis 



excretion 

 in faeces 



POLIOMYELITIS 



Fig. 1. Schematic diagram showing the mode of spread of mousepox virus and polio- 

 virus in the host after infection by natural routes (modified from Fenner, 1956). 



In a great many infectious diseases there is a stage of initial infection 

 (which may be symptomless), a relatively long incubation period, and then a 

 stage of generalization with toxic symptoms and symptomatic involvement of 

 some particular organs or tissues, such as the skin (the exanthemata), the 

 central nervous system (the encephalitides and poliomyelitis), or certain 

 glands (mumps). In such diseases, the symptoms (and hence the assessment 

 of virulence) do not depend on multiplication of the virus at the site of entry 

 but upon multiplication at a number of distant sites. 



Mousepox (infectious ectromelia of mice) has provided a model for a study 

 of a sequential infection culminating in a rash (Fenner, 1948a). The scheme 

 proposed, and its later extension to cover poliomyelitis (Fenner, 1956) are 

 shown in Fig. 1. 



