Disease had plagued the population of all major port cities on the coast of the American colonies due to the sudden introduction of many foreign people and their foreign diseases into the New World. Diseases from Europe and Africa were introduced by maritime travel. Without immunity to diseases like malaria, smallpox, tuberculosis, and cholera, an infection could become an epidemic, quickly spreading through the colonial population. To limit the spread of such communicable diseases, arriving vessels, passengers, and cargo were inspected before they entered the city. Pestilence houses or "lazaretto" – named for Saint Lazarus the patron saint of lepers – were established to hold the infected passengers for ten to forty days to avoid contamination of the public.
Charles Towne's erected one of the earliest colonial pestilence houses on Sullivan's Island in 1707. Made of brick without a ceiling, insulation, or windows, the building measured 30x16 feet and offered little comfort or medical care for the sick. A total of four pestilence houses stood on Sullivan's Island during the eighteenth century. None survive today and their original locations are undetermined but it is known that they occupied lots between Fort Moultrie and the west end of the island. In 1793, Sullivan's Island residents called for the removal of the pestilence house. The last pestilence house located on the island was closed and sold in 1796. The pestilence houses were relocated to James Island and later, in the 1830's, to Morris Island.
Although the exact locations of the pestilence houses on Sullivan's Island are unknown, but their importance to Fort Moultrie's history connects them forever. However, one remaining lazaretto still exists outside of Philadelphia. This gives visitors a chance to contemplate the experience of immigrants once they arrived in America.