Leptospirosis is transmitted by direct contact with the body fluid of an acutely infected animal or by exposure to soil or water that has been contaminated with urine from an animal (bovine, murine, or canine) that is a chronic carrier. The disease can be acquired occupationally, during travel or vacations that involve water sports or hiking, or as a consequence of flooding. The leptospires enter the host through skin abrasions, intact mucous membranes or conjunctiva, the nasal mucosa and cribriform plate, the lungs (after inhalation of aerosolized body fluid), or the placenta during pregnancy. Organisms travel to the bloodstream through the lymphatics and can multiply in the small blood vessel endothelium, resulting in leptospiremia and multiorgan involvement. The incubation period is generally 5 to 14 days but can be as short as 72 hours or as long as a month or more.

Complications include interstitial nephritis, tubular necrosis, septicemia, hypovolemia, shock, vasculitis, secondary infection, disseminated intravascular coagulation (DIC), hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, and multiorgan failure. Pulmonary involvement results in hemorrhage and is the major cause of leptospirosis-associated death.

Initially, an acute illness begins with high fever, rigors, sudden headache, nausea and vomiting, anorexia, diarrhea, cough, pharyngitis, nonpruritic skin rash, and muscle pain. Myalgia often affects the calf and lumbar areas. This phase lasts 5 to 7 days and either regresses to a relatively asymptomatic period or progresses to a more severe illness. When fever is severe and prolonged, hypotension and shock can occur. Petechial eruptions of the palate, jaundice, purpura, reddened conjunctiva (without exudate), and uveitis follow acute leptospirosis. Signs of meningitis (neck stiffness and rigidity, photophobia) and cardiac-related pulmonary edema (rales and wheezes) can occur. Myocarditis may occur in severe disease, with signs of biventricular heart failure and arrhythmias. Abdominal examination may reveal liver enlargement and tenderness due to hepatitis; cholecystitis and pancreatitis may also be present in severe cases. Heme-positive stool and bleeding on rectal examination occurs with DIC. Delirium may be an early finding in severe disease; depression, anxiety, irritability, psychosis, and even dementia can persist in the convalescent phase.