Typhus exanthematicus is an old disease long confused with typhoid fever. Some historians believe that it caused the Plague of Athens as described by Thucydides, and that it was introduced into Europe by the Spanish soldiers returning from the Americas in the sixteenth century. It likely caused the severe epidemic occurring during the confrontations between the Spanish Christians and the Moors, and it subsequently ravaged the armies and civilian populations during the Thirty Years’ War (1618–1648). Typhus contributed to the defeat of the French during Napoleon’s Russian invasion in 1812.

Typhus outbreaks typically occurred in unsanitary, crowded military barracks, prisons, and refugee camps. A major typhus epidemic struck Ireland between 1816 and 1819, and the disease was particularly deadly during the Irish Potato Famine of 1846–1849 and during the two World Wars, when it spread rapidly and killed millions of soldiers and civilians. It was rampant in Russia during the late 19th and early 20th centuries and claimed countless lives in the Nazi concentration camps of World War II, exacerbating the horrors of the Holocaust. Anne Frank and her sister Margot died of typhus fever in the Bergen-Belsen concentration camp in February 1945.

The name typhus comes from the Greek word meaning smokey. Thomas Willis (1622–1675) distinguished it from typhoid fever and so did Pierre Louis (1829) who coined the term “typhoid fever.” Sir William Jenner (1852–1898) also played a significant role in differentiating the two diseases, particularly in his role as Physician in Ordinary to Queen Victoria.

Working at the Pasteur Institute in Tunis in 1909, the French physician Charles-Jules-Henri Nicolle made an important advance by using chimpanzees as experimental animals and proving that typhus was transmitted from person to person by the feces of the body louse, Pediculus humanus corporis. Nicolle won the Nobel Prize in 1928.

The cause of the disease was discovered in 1916 by Henrique da Rocha Lima, a Brazilian doctor who named it Rickettsia prowazekii in memory of his colleague, Stanislaus von Prowazek. Both physicians had been infected while studying the organism’s transmission. Rocha Lima survived, but von Prowazek died from typhus in 1915.

The organism causing typhus is a Gram-negative intracellular bacterium related to Rocky Mountain spotted fever, epidemic typhus, scrub typhus, murine typhus, and African tick-bite fever. There is also a relapsing form of epidemic typhus called Brill-Zinsser disease, in which some infected persons retain the bacteria in a latent form for the rest of their lives and after many years have a recrudescence of the disease. During World War II, the development of the insecticide DDT (dichlorodiphenyltrichloroethane) and mass delousing campaigns controlled the lice populations and marked a turning point in the fight against the disease. Epidemic typhus is now rare in developed countries but remains a concern in regions experiencing war, displacement, and poor sanitation. Outbreaks have been reported in parts of Africa, South America, and Eastern Europe, where conditions favor the proliferation of body lice. Advances in antibiotics, particularly doxycycline, have made typhus a treatable disease. Early diagnosis and intervention remain crucial to preventing severe complications. Public health efforts continue to focus on improving sanitation, controlling lice infestations, and providing medical care to affected populations, hoping to make typhus exanthematicus truly a disease of the past.