Two major clues suggest epidemic typhus. The first is the character and evolution of the rash, which consists of macular lesions that spread centrifugally but spare the palms, the soles, and the face. The IFA assay may be the most sensitive of available tests for epidemic typhus. Both chloramphenicol and a tetracycline administered in dosages identical to those prescribed for RMSF are effective in the treatment of epidemic typhus. The patient usually becomes afebrile in 48 hours.
Relapses are rare even if treatment is started as early as the first or second day of the illness.
The use of doxycycline in a single 100 mg dose in field conditions for the treatment of classic epidemic typhus has resulted in defervescence and resolution of symptoms. A commercially available killed rickettsial vaccine derived from infected yolk sac tissue is effective in preventing epidemic typhus or at least in ameliorating the course of the disease if it does occur. In untreated cases, mortality is age related. Use of broad-spectrum antibiotics before irreversible changes occur has reduced mortality to a negligible rate.