EXPERIMENTAL EPIDEMIOLOGY OF TUBERCULOSIS : THE EFFECT OF ELIMINATING EXPOSURE TO ENTERIC INFECTION ON THE INCIDENCE AND COURSE OF TUBERCULOSIS ACQUIRED BY NORMAL GUINEA PIGS CONFINED WITH TUBERCULOUS CAGE MATES.

In these studies normal guinea pigs were exposed to tuberculous cage mates in two different degrees of crowding, some in ordinary cages, where the food became contaminated with the excreta, laden with tubercle bacilli, of the inoculated animals, and some in special cages with wire-mesh floors, where these excreta were largely excluded as a source of contagion. The results are summarized in Table V. In all these experiments crowding has always increased the incidence of the disease both in the ordinary and the special cages. However, due to the accident of eating of tuberculous animals in the more crowded cages these results are not conclusive, but they are in accord with the results of the previous study (2). It was found that the incidence of tuberculosis was lower among the guinea pigs exposed to contagion in the special cages, in which little of the contaminated excreta remained in direct contact with the normal animals. In fact in the less crowded special cages the incidence of tuberculosis was only a little higher than among the same total number of guinea pigs exposed at the same time in the same room but not confined with tuberculous cage mates. In the special cages, especially in the less crowded, where nearly all the contaminated excreta were removed, the disease acquired was largely respiratory in origin and was characterized by an extensive tuberculosis of the tracheobronchial lymph nodes with little or no affection of the mesenteric nodes. The pulmonary disease in the guinea pigs that acquired tuberculosis in these cages was more often extensive than that acquired in the ordinary cages. However no definite evidence of primary lesions in the lung in the former was found, due to the dissemination of the disease at the time of death. The tuberculosis acquired by the contacts in the ordinary cages, on the other hand, was usually enteric in origin, although both routes were involved, especially in the less crowded cages. Moreover, a striking fact appears if we compare the course of tuberculosis in these two types of cages in both degrees of crowding: the contacts that developed tuberculosis in the ordinary cages survived an average of 106 and 114 days longer than the corresponding animals in the special cages. It is well known that the respiratory route is a far more dangerous avenue of infection in tuberculosis than the alimentary canal. This fact has again been clearly brought out in the recent studies of Bruno Lange and his associates (3), who have shown that although guinea pigs may occasionally be infected by way of the mouth with quantities as low as 0.000,001 mg. of virulent tubercle bacilli they often escape infection even when fed 0.1 mg. or more. On the other hand if guinea pigs are made to inhale even the smallest quantities of tubercle bacilli they regularly contract tuberculosis. Furthermore they have also shown that the alimentary infection produces a disease far more chronic in character than that acquired by the respiratory route. It would therefore seem that the more acute type of disease is acquired in the special cages because in these cages the respiratory route plays by far the more important rô1e whereas in the ordinary cages the disease is largely of enteric origin. However, it appears that in the ordinary cages where the guinea pigs were constantly stirring up their sawdust or peat-moss bedding, laden with tubercle bacilli, there was an even greater opportunity for respiratory infection than in the special cages where there was no bedding at all and where most of the excreta were removed from immediate contact with the normal animals. That the respiratory mode of infection plays a rô1e even in the ordinary cages was shown in a previous communication (2) as well as in this paper. In both studies it was found that only in the more crowded ordinary cages is the disease almost entirely of enteric origin but in the less crowded ordinary cages infection takes place by the respiratory tract as well, though to a smaller degree than by the alimentary. It would therefore appear that in the ordinary cages both routes are open for infection but the relatively larger doses of tubercle bacilli ingested determine a disease of enteric origin and hence of a chronic nature, suppressing at the same time the engrafting of the disease by way of the lungs, and that in the special cages where the alimentary sources of infection have been reduced to a minimum, the disease is engrafted by way of the lungs and is therefore of more acute type. Although in the special cages the intensity of exposure even to tubercle bacilli entering by the respiratory tract is less than in the ordinary cages, nevertheless the disease so produced is more acute, presumably because the inhibitory or retarding effect of enteric infection upon the development of respiratory disease is absent. This explains the paradoxical effect observed of a greater incidence and a more chronic type of disease in the ordinary cages and a lower incidence and a more acute type of disease in the special cages, for the intensity of exposure by both routes is greater in the ordinary cages, and of the two, much greater by the enteric route.