In the early 1900s, it is finally determined that the cause of yellow fever is a mosquito called Aedes Aegypti. More specifically, it is the female who spreads the disease because she requires human blood, whereas the male does not. In 1793, infected mosquitoes are most likely carried on ships that docked in Philadelphia. The city’s open wells, water barrels, and sewers make ideal breeding grounds for the infected mosquitoes to reproduce and spread the disease.

Once the mosquito is identified as the cause, people can take better precautions to stop the spread, such as placing netting around encampments of the infected. Attempts are made in the 20th century to rid the Western Hemisphere of Aedes Aegypti by spraying pesticides, but they are unsuccessful and eventually raise concerns over health risks.

Bush Hill is an abandoned mansion that the mayor, along with the Overseers and Guardians of the Poor, decide to turn into a hospital for yellow fever patients. The owner is in England and the caretaker is unable to stop them from taking control of the mansion. The hospital is set up a few weeks after the disease begins to spread and is initially very disorganized and poorly run.

However, wealthy merchant Stephen Girard and barrel maker Peter Helm soon step in to manage the hospital.