The diphtheria bacilli have a pathogenic action on lower animals only when introduced artificially. Tf the tracheal mucosa of a rabbit is injured by traumatism and the bacilli injected, the animal dies with symptoms similar to those in membranous croup. At the autopsy a fibrinous, luemorrhagic exudate is found on the trachea. The mucosa around the site of the inoculation is strongly reddened and covered with a grayish yellow, thick, tenacious pseudomembrane, from which the bacilli can be cultivated. Identical appearances follow if, instead of the bacilli, a germ-free filtrate of a culture is used for the injection, one being chosen which does not cause death too suddenly (Roux, Roger and Bayeux. Trump') and Ziegler). Control-animals recover from the trau matism very promptly and the mucosa shows only small red deposits. While the animals in such experiments (lie from obstruction of the trachea, when the bacilli or the toxin are injected subcutaneously or int•aperitoneally the animals die with symptoms of general intoxication and if the course is prolonged, paralyses occur which resemble the post diphtheritic paralyses in human beings.
The typical findings are fibrinous exudate at the site of injection, inflammation of the serous membranes and hyperaemia of the adrenals. If the bacilli are injected they are found only at the site of inoculation. Death can therefore be the result only of intoxication. The fact that the pseudomembran-es which follow the injection of bacilli are also caused by on injection of the germ-free toxin proves that their development is to be attrib uted to the action of the poison.
In the animals which survive the injections there is found an in creased resistance to the action of further doses of the toxin, but this acquired immunity to the poison does not prevent the possibility of diphtheria bacilli obtaining a foothold and multiplying on the mucous membranes. On the ability to transfer from animal to animal and from animal to moan this condition of immunity rests Behring's serum therapy.
Not all of the Loffler bacilli are pathogenic. Their virulence, or the ability of their protoplasm to produce toxin is very different (but not necessarily so) in that bacilli from mild cases are less virulent than those from severe cases. The results of animal experiments and clinical obser vation often harmonize, but not always. This lack of harmony is prob ably due to the variations in the living material, and also sometimes to chance in the experimentation. The bacilli cultivated from one case do not all show the same degree of power, as virulent and non-virulent may be found side by side. The latter either show all the characteristics typical of the LHler bacillus, or vary somewhat in their morphological or cultural peculiarities, which has led Loftier, Hoffmann-Wellenhof, Escherich and others to view them as a special kind of bacilli, the pseudo diphtheria bacilli. But since it has been possible by a passage through animals, whose resistance has been lowered by non-fatal doses of diph theria toxin, to change typical pseudodiphtheria bacilli into highly viru lent diphtheria bacilli, typical morphologically as well as culturally (Trumpp), they can no longer be considered a distinct species.
This experiment also throws interesting light on the activity of other bacteria which accompany the diphtheria bacilli in the so-called mixed infections. The latter are looked upon mainly as secondary processes in which pyogenic cocci and bacteria of putrefaction play the main role. We cannot. yet grant that they enter into a kind of symbiosis with the bacilli and thereby increase the virulence of the latter (Roux) but rather that their entrance into the tissues and fluids is made possi ble by the activity of the diphtheria bacilli, and that the cocci in turn lower the resistance of the organism to the bacilli or their toxin. They can be looked on as sharers in the disease-process only when they are deep in the pseudomembrane or in the submucous tissues, but not if they are only lying on the pseudomembrane, for dozens of species of streptococci and staphylococci are included among the common inhabi tants of the mouth and are found, in consequence, also in the superficial layers of the false membrane. When the mixed infection is streptococcal, the symptoms are like those of other septic processes. According to Bcrnheim, blood-infection is not always necessary, as the process need not advance further than an intoxication, the streptococci remaining in the false membrane while their toxins are absorbed. The result then is a combined action of the toxins of the diphtheria bacilli and streptococci.
In almost all cases which show the clinical course of diphtheria LOffler bacilli are found in the local deposit. As a rule they are found only in the necrotic tissue and exudate, in the lymph-spaces and the regional lymph-nodes. Instances of the bacilli in the blood during life or in the blood and internal organs after death are extremely rare. Some time after the decline of the attack, the bacilli disappear from the pharynx but they may remain for weeks and months capable of multiplying, and in a virulent state, on other mucous membranes, in the nasal passages, on the conjunctiva or the vulva. The bacilli arc spread from one person to another by contact with the sick and convalescent and also by arti cles and food infected by them (milk). It is now fully established that virulent Loffler bacilli can settle on the mucous membranes of healthy persons without causing symptoms of the disease; and so frequently have bacilli which belong beyond doubt to the family of Corynebacter ium diphtheria been found in the nose and on the conjunctiva of chil dren and adults who, so far as is known, have not been in contact with diphtheria patients, that the diphtheria bacillus may be considered al most ubiquitous. These considerations show us that the mere presence of the bacilli is not sufficient for the development of the disease.