As the rats begin to die off, their fleas resort to biting humans and transmit the disease to them. Apparantly the bacteria can multiply in the intestinal tract of the flea to such high concentrations that the intestinal tract of the insect becomes blocked, and the bacteria are regurgitated into the bite wound produced as the flea frantically tries to get blood from its mammalian host to its intestine. In the human, the organisms are transmitted to the regional lymph nodes and, if phagocytosed by macrophages, survive and become fully virulent for a wide variety of human cells. If the lungs are infected by aerosol transmission, pneumonic plague develops. This is directly transmissible to other humans via the respiratory route, although this is thought to be relatively rare.
Pneumonic plague is rapidly fatal due to hemorrhagic necrosis of the lung and resulting cyanosis.
In bubonic plague, multiplication of the organism in the lymph nodes produces the characteristic buboes. If untreated, septicemia occurs and death is due to endotoxic shock.