1. The Virulence of the Infecting Organisms and the Amount Introduced.

—There is the widest difference between various forms of microörganisms in the matter of virulence; and it is true that there are very great differences between the same species under different circumstances, these differences depending on conditions as yet absolutely unknown. With certain organisms it is enough to infect an animal with one alone in order to bring about a fatal result, this meaning that the organism itself is extremely virulent and the animal extremely susceptible.

In a guinea-pig, for instance, a single virulent anthrax bacillus will produce death, whereas in a more resistant animal many are required, and in still others there is absolute immunity against the disease. Man is much more susceptible to the pyogenic organisms than most of the lower animals, which is one reason why wrong deductions have been drawn from many experiments, and why veterinary surgeons, who are so careless of all antiseptic precautions, as a rule have good results in work which, done after the same fashion on the human being, would be inevitably fatal. It is one reason also why one may draw false inferences from experimental work, for instance, upon dogs, which survive many an operation which can scarcely be successfully repeated upon a human being. The influences which affect the vitality and virulence of microörganisms are most numerous and widespread. Temperature, sunlight, moisture or dryness, association with other bacteria, are but a few of the conditions known to be more or less operative. Inoculation with a small number of certain bacteria may be harmless; up to a certain number it may produce only a local disturbance, like abscess, while a still larger dosage may produce fatal results. This is not the case with all, however, but only with some organisms. Bacteria which have been repeatedly passed through the animal body become more virulent than those cultivated for many generations in test-tubes in the laboratory. This variable virulence is especially characteristic of the colon bacillus, the anthrax bacillus, and the micrococcus of erysipelas. Nor does it always follow that the most virulent organism is necessarily cultivated from the most toxic or serous manifestation of its activity.

2. Association.

—Bacteria are seldom found in pure cultures under natural conditions. By mutual association remarkable changes are produced, sometimes in the direction of enhanced virulence, sometimes in the direction of attenuation of effect. Certain organisms, extremely dangerous alone, lose their power when combined with others, while still others have their virulence increased to a rapidly fatal degree. In fact, these effects are so strange and so contradictory that no law governing them has yet been formulated, it being necessary to establish each case by experimental investigation. The virulence of the anthrax bacillus under ordinary circumstances is well known, as is also that of the streptococcus of erysipelas in man. Yet, when these two organisms are introduced simultaneously, the mixture is apparently wellnigh harmless. On the other hand, the simultaneous inoculation of certain other species greatly increases the danger from either alone. The diplococcus pneumoniæ when combined with the anthrax bacillus seems to have a greatly augmented power.

3. Hereditary Influences.

—The fact that immunity against certain infections and susceptibility to other conditions are transmitted from parent to offspring is one which admits of no dispute. The explanation, however, is almost as remote from us today as it ever was. But the recognition of the fact is of the greatest importance to all practising surgeons. That bacteria frequently enter through wounds and bruises is self-evident, but we all know that such wounds are more likely to suppurate in some than in others, and the causes of infection in some are, to a certain extent, connected with the hereditary habit of tissues. The same causes influence not merely liability to infection, but its severity and character. There are undoubtedly also local as well as general variations, and it is very certain that among these the results of bruising or contusion are by far the most prominent. There is also undoubted experimental evidence that under certain circumstances bacteria produce only local lesions, whereas under others they produce general and even fatal infection.

4. Local Predisposition.

—Local predisposition is a factor of almost equal importance. Once given a distinct infection, and hyperemia is sometimes a contributing cause of inflammation. Per contra, anemia of tissues seems to be also a favoring condition. In parts involved in chronic congestion the blood flows more slowly, while the vessels are dilated and apparently susceptibility is increased. Infection here produces a type of disease mentioned as hypostatic inflammation. Conspicuous exception as to the occasional value of an artificial passive hyperemia is seen, however, in the so-called congestion treatment (Bier’s) of tuberculous joints, where the more or less constant flooding of the tissues with venous blood seems to render them uninhabitable for living bacilli, which apparently die and disappear (by phagocytosis), thus permitting a slow return to the normal condition. General anemia, again, is a predisposing cause, while toxemias, including diabetes, etc., are still more so. The liability of diabetic patients to suppurative and even gangrenous infection is proverbial. The presence of foreign bodies has much to do also, and, infection once having occurred along with its introduction, the presence of a foreign body will nearly always excite suppuration; otherwise it will ordinarily remain inert. The withdrawal of trophic nerve influences also apparently permits infection, as is instanced by the ease with which bed-sores form in paralytic patients. Obstruction to the circulation or to escape of secretions more easily permits infection; for example, in the appendix, in the kidney, in the gall-bladder, the salivary glands, etc. Furthermore, one may formulate a quite comprehensive statement and say that all such lesions as solutions of continuity, hemorrhages, degenerations, vascular stasis produced by strangulation, etc., and all perforations, increase more or less the liability to infection.

5. Pre-existing Disease.