450 Pathogenesis of Undulant Fever 



endothelial beds in the organs. Loffler and v. Albertini'' specifically place the 

 focal processes in the spleen and liver. This interpretation of the pathogenesis 

 is largely based on the fact that the characteristic "tuberculoid, nodular" 

 lesions or "granulomas" are principally noted in these organs and the culti- 

 vation of the organism from these tissues is frequently successful. Their pres- 

 ence in the lymph nodes is believed to be secondary and not the resultant of 

 hematogenic invasion. The explanation by Loffler-' has a great deal of plausi- 

 bility. In uncomplicated Brucella deaths the spleen is regularly enlarged; 

 furthermore, the majority of clinicians have found the spleen palpable in 

 varying degrees. The German data mention this sign in 80 per cent of the 

 cases; on the other hand, Simpson,^' and Hardy and associates* found a splenic 

 tumor in only 30 per cent of their observations. Thus, there is no justification 

 for considering the splenic tumor as an obligatory sign of brucellosis. The 

 liver is enlarged even less frequently (German data 20 per cent; 4 per cent in 

 Simpson's cases). No correlations between the enlargement of these organs 

 and the blood-culture findings are available. 



Nothing is known concerning focal seedbeds in the bone marrow; both 

 Wohlwiir and Wegener" have found epithelioid nodules and even necroses. 

 Even the best culture methods used repeatedly and by experienced workers 

 have yielded negative blood cultures. It is, therefore, not unlikely that other 

 factors than the bacteremia are responsible for the febrile reactions. Since 

 true toxins of the Brucella organism have not as yet been demonstrated, one 

 has to think of the proteolytic degradation of the harmless albuminoid body 

 substances to poisons or the formation of febrigenic substances to poisons from 

 the tissties of the infected host through autolysis. These poisons in turn gen- 

 erate new foci of inflammation, and thus fever-inducing factors are created 

 without the actual proliferation and dissemination of the specific bacteria 

 which initiated the disease. A series of febrile elevations of the body tempera- 

 ture may not be accompanied by or induced by a bacteremia. 



Finally, there is the possibility that the symptoms are manifestations of the 

 allergic state which always develops in the course of a brucellosis. The paren- 

 teral presence of the bacterial elements as antigens stimulates the production 

 of antibodies in the tissues, and these in turn come in contact with the bacterial 

 protein which is liberated during the disintegration of the bacteria in the 

 various phagocytes. Through interaction of these two components a disease- 

 producing agent may be formed. Obviously, it is subject to discussion as to how 

 these substances are formed: the combination may produce the poison, the 

 disintegration of the bacterial protein may liberate an injurious substance, 

 or the evolution of the antibody per se may represent the noxis. In Brucella 

 infection, just as in tuberculosis or in fungus disease, the allergy factor plays 

 an important role in the mechanism of immtuiity, and a fair portion of the 

 symptomatology may be conditioned by this altered state of reactivity. 



All these attempts to explain the pathogenesis of a Brucella infection leave 

 out of consideration the primary question: Does the organism lead an intra- 



