Epidemic typhus (louse-borne typhus) is caused by infection with Rickettsia prowazekii, transmitted to humans by body lice typically found in conditions of poor hygiene. Wartime, famine, or overcrowded conditions such as with cold weather favor proliferation of the louse vector. Mortality is variable but is increased in the aged and when anti-rickettsial therapy is delayed.

Weaponized epidemic typhus would most likely be aerosolized, but release of infected lice is a feasible alternative. After a 7-day incubation period, abrupt onset is heralded by intense headache and unremitting high fever (39ºC-40ºC). Chills, myalgias, and prostration are common, and a non-productive cough may also be present. After 5 days, a macular, popular, and/or petechial rash appears. Meningismus is rarely reported, although central nervous system involvement may include confusion, delirium, and coma. Tinnitus and deafness have been reported. Renal insufficiency, pneumonia, and multiple organ failure may ensue. Full recovery may take months.

In the United States, an animal reservoir of R. prowazekii exists in the southern flying squirrel, which is found in eastern regions and as far west as Minnesota to eastern Texas. At least 15 human cases have been diagnosed serologically. Transmission among squirrels is believed to be via squirrel lice or fleas, and while the squirrel has been implicated as a reservoir, the responsible vector for human disease is unclear.

Epidemic typhus is also seen in rural highlands of Central and South American as well as in Africa (Ethiopia in particular).