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Hantavirus infections in humans are associated with two diseases: hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome , caused by Old World and New World hantaviruses, respectively. A common feature of the two diseases is increased vascular permeability, which causes hypotension, thrombocytopenia, and leukocytosis. The pulmonary illness is the more fatal of the two, whereas the hemorrhagic fever is much more common. Treatment for both is primarily supportive as there is no specific treatment for hantavirus infections. While many hantaviruses cause either of the two diseases, some are not known to cause illness, such as the Prospect Hill orthohantavirus.

Hemorrhagic fever with renal syndrome is caused chiefly by hantaviruses in Asia and Europe. Clinical presentation varies from subclinical to fatal, depending on the virus. After an incubation period of 2–4 weeks, the typical illness starts with non-specific symptoms such as high fever, chills, headache, backache, abdominal pains, nausea, and vomiting. After the initial period, bleeding under the skin begins, often paired with low blood pressure, followed by further internal bleeding throughout the body. Renal dysfunction leading to further health issues begins thereafter, which may cause death. A more mild form of HFRS that occurs in Europe is called "nephropathia epidemica". Trench nephritis during World War I is now thought to have been HFRS.

Hantavirus pulmonary syndrome , also called hantavirus cardiopulmonary syndrome , is usually caused by hantaviruses in the Americas. Its incubation period ranges from 16 to 24 days. Illness initially shows similar symptoms as HFRS. After a few days of non-specific symptoms, sudden onset of progressive, or productive, coughing, shortness of breath, and elevated heart rate occur due to fluid buildup in the lungs. These symptoms are accompanied by impairment of lymphoid organs. Death from cardiovascular shock may occur rapidly after the appearance of severe symptoms. While HCPS is typically associated with New World hantaviruses, the Puumala orthohantavirus in Europe has also caused the syndrome on rare occasions.

Hantaviruses are transmitted by contact with the bodily fluids of rodents, particularly from saliva from bites and especially from inhalation of viral particles from urine and feces in aerosols. The manner of transmission is the same for both diseases caused by hantaviruses. Among the HCPS-causing hantaviruses is the Andes orthohantavirus, which is the only hantavirus confirmed to be capable of spreading from person to person, though this is rare.

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