Infection can take place only when the micro-organisms are sufficiently virulent, when they enter in sufficient number, when they enter by appropriate avenues, and when the host is susceptible to their action.

Virulence refers to the disease-producing power of microorganisms which depends upon the invasiveness of the bacteria, the toxicity of their products, or both. This property may vary greatly in different strains of the same variety of organism. Most bacteria when grown in artificial media will not be as virulent as those grown in some animal. If, however, animal fluids are added to the culture-media the virulence may be retained or even increased. In order to increase the virulence, the best results can be obtained by the transplantation of the organism from one animal to another without any intermediate growth on culture-media. This method, however, increases the virulence of the organism only for that particular kind of animal used. Transference through rabbits increases the virulence for rabbits, but not for other kinds of animals. This increase can continue to a certain point, beyond which it will not go. The number of organisms which is necessary to kill the animal becomes progressively smaller, and the period of incubation, the time between infection and the first symptoms, shorter, until finally a strain is obtained in which the degree of virulence can no longer be increased by animal passage. This constitutes the "virus fixe".

Number

The number of bacteria gaining entrance has a very important bearing upon infection, and may determine whether it shall occur or not. When bacteria gain entrance into an animal there will always be some of the organisms that are unable to withstand the defensive powers of the host, and consequently perish. Others may be so weakened as to be unable to cause trouble, while some will be able to overcome the resistance, and give rise to disease. The more virulent the organism, the fewer will be the number required to infect.