There is an abrupt onset of fever, chills, tachycardia, nausea and vomiting, arthralgia, and severe headache. Hepatomegaly and splenomegaly may develop, as well as various types of rashes (macular, papular, petechial) that usually occur at the end of a febrile episode. Delirium occurs with high fever, and there may be various neurologic and psychological abnormalities. The attack terminates, usually abruptly, after 3–10 days. After an interval of 1–2 weeks, relapse occurs, but often it is somewhat milder. Three to ten relapses may occur before recovery in tick-borne disease, whereas louse-borne disease is associated with only one or two relapses.
During episodes of fever, large spirochetes are seen in thick and thin blood smears stained with Wright or Giemsa stain. The organisms can be cultured in special media but rapidly lose pathogenicity. The spirochetes can multiply in injected rats or mice and can be seen in their blood.
A variety of anti-Borrelia antibodies develop during the illness; sometimes the Weil–Felix test for rickettsioses and nontreponemal serologic tests for syphilis may also be falsely positive. Infection can cause false-positive indirect fluorescent antibody and Western blot tests for Borrelia burgdorferi, causing some cases to be misdiagnosed as Lyme disease. PCR assays can be performed on blood, CSF, and tissue but are not always available in endemic regions. CSF abnormalities occur in patients with meningeal involvement. Mild anemia and thrombocytopenia are common, but the white blood cell count tends to be normal.