These zoonotic infections are severe febrile diseases in which shock and bleeding can be significant and multisystem involvement can occur. In the United States, one of these infections causes an illness marked by acute respiratory and cardiovascular failure (see Hantavirus Pulmonary Syndrome).

Hemorrhagic fever with renal syndrome (HFRS) is a complex, multiphasic disease characterized by vascular instability and varying degrees of renal insufficiency. Fever, flushing, conjunctival injection, abdominal pain, and lumbar pain are followed by hypotension, oliguria, and subsequently, polyuria. Petechiae and more serious bleeding manifestations are common. Shock and acute renal insufficiency may occur. Nephropathia epidemica, the clinical syndrome of HFRS in Europe, is a milder disease characterized by an influenza-like illness with abdominal pain and proteinuria. Acute renal dysfunction also occurs, but hypotensive shock or a requirement for dialysis are rare.

Crimean-Congo hemorrhagic fever (CCHF) is a multisystem disease characterized by hepatitis and profuse bleeding. Fever, headache, and myalgia are followed by signs of a diffuse capillary leak syndrome with facial suffusion, conjunctivitis, and proteinuria. Petechiae and purpura often appear on the skin and mucous membranes. A hypotensive crisis often occurs after the appearance of frank hemorrhage from the gastrointestinal tract, nose, mouth, or uterus.

Rift Valley fever (RVF) , in most cases, is a self-limited febrile illness. Occasionally, hemorrhagic fever with shock and icterus, encephalitis, or retinitis develops.