In 1796 a trading ship arrives in the vibrant harbor town of Newburyport, Massachusetts, her crew decimated by a virulent fever. Despite the ship being placed under quarantine, this mysterious disease sweeps through the waterfront, causing entire families to die of plague-like symptoms with alarming haste. Dr. Giles Wiggins, a surgeon and veteran of the American Revolution, works tirelessly to save lives, often disagreeing with his medical colleagues on both the cause of the deadly ailment and its remedy. As the epidemic grows, the seaport's future is threatened by mayhem, greed, and fear.