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Hantavirus Infection

by Craig R. Pringle, BSc, PhD

Bunyaviridae contain the genus Hantavirus, which consists of at least 4 serogroups with 9 viruses causing 2 major, sometimes overlapping, clinical syndromes:

  • Hemorrhagic fever with renal syndrome (HFRS)

  • Hantavirus pulmonary syndrome (HPS)

Viruses causing HFRS are Hantaan, Seoul, Dobrava (Belgrade), and Puumala. Those causing HPS are Sin Nombre, Black Creek Canal, Bayou, and New York-1.

Hantaviruses occur throughout the world in wild rodents, which shed the virus throughout life in urine and feces. Transmission occurs between rodents. Transmission to humans is through inhalation of aerosols of rodent excreta. Recent evidence suggests human-to-human transmission may occur rarely. Naturally and laboratory-acquired infections are becoming more common.

Laboratory diagnosis of hantavirus infection is established by serologic tests and reverse transcriptase–PCR (RT-PCR). Serologic tests include enzyme-linked immunosorbent assay (ELISA) and Western and strip immunoblot assays. Growth of the virus is technically difficult and requires a biosafety level 3 laboratory.

Hemorrhagic Fever With Renal Syndrome (HFRS)

(Epidemic Nephrosonephritis; Korean Hemorrhagic Fever; Nephropathia Epidemica)

Hemorrhagic fever with renal syndrome (HFRS) begins as a flu-like illness and may progress to shock, bleeding, and renal failure. Diagnosis is with serologic tests and PCR. Mortality is 6 to 15%. Treatment includes IV ribavirin.

Some forms of HFRS are mild (eg, nephropathia epidemica, caused by Puumala virus, as occur in Scandinavia, the western part of the former Soviet Union, and Europe). Others are severe (eg, those caused by Hantaan, Seoul, and Dobrava viruses, as occur in Korea or the Balkans).

Symptoms and Signs

Incubation is about 2 wk. In mild forms, infection is often asymptomatic.

When symptoms occur, onset is sudden, with high fever, headache, backache, and abdominal pain. On the 3rd or 4th day, subconjunctival hemorrhages, palatal petechiae, and a truncal petechial rash may appear. Diffuse reddening of the face that resembles sunburn, with dermatographism, occurs in > 90% of patients. Relative bradycardia is present, and transient mild hypotension occurs in about half of patients, with shock in a minority. After the 4th day, renal failure develops.

About 20% of patients become mentally obtunded. Seizures or severe focal neurologic symptoms occur in 1%. The rash subsides; patients develop polyuria and recover over several weeks. Proteinuria, hematuria, and pyuria may develop.


  • Serologic testing or PCR

HFRS is suspected in patients with possible exposure if they have fever, a bleeding tendency, and renal failure. CBC, electrolyte levels, renal function tests, coagulation tests, and urinalysis are then done. During the hypotensive phase, Hct increases and leukocytosis and thrombocytopenia develop. Albuminuria, hematuria, and RBC and WBC casts may develop, usually between the 2nd and 5th day. During the diuretic phase, electrolyte abnormalities are common.

Diagnosis of HFRS is ultimately based on serologic testing or PCR.


Death can occur during the diuretic phase, secondary to volume depletion, electrolyte disturbances, or secondary infections. Recovery usually takes 3 to 6 wk but may take up to 6 mo. Overall, mortality is 6 to 15%, almost always occurring in patients with the more severe forms. Residual renal dysfunction is uncommon except in the severe form that occurs in the Balkans.


  • Ribavirin

  • Sometimes renal dialysis

Treatment is with IV ribavirin: loading dose 33 mg/kg (maximum, 2.64 g), followed by 16 mg/kg q 6 h (maximum, 1.28 g q 6 h) for 4 days, then 8 mg/kg q 8 h (maximum, 0.64 g q 8 h) for 3 days. Supportive care, which may include renal dialysis, is critical, particularly during the diuretic phase.

Hantavirus Pulmonary Syndrome (HPS)

Hantavirus pulmonary syndrome (HPS) occurs in the US primarily in the southwestern states. It begins as a flu-like illness and, within days, causes noncardiogenic pulmonary edema. Diagnosis is with serologic tests and reverse transcriptase–PCR. Mortality is 50 to 75%. Treatment is supportive.

Most cases of HPS are caused by the Sin Nombre hantavirus (Four Corners virus, Muerto Canyon virus); others are caused by the Black Creek Canal virus or Bayou virus in the southeastern US, the New York virus on the East Coast of the US, or the Andes virus or Laguna Negra virus in South America. Infection is transmitted to humans via inhalation of excreta of sigmodontine rodents (especially the deer mouse). Most cases occur west of the Mississippi River in spring or summer, typically after heavy rains.

Symptoms and Signs

HPS begins as a nonspecific flu-like illness, with acute fever, myalgia, headache, and GI symptoms. Two to 15 days later (median 4 days), patients rapidly develop noncardiogenic pulmonary edema and hypotension. Several patients have had a combination of HFRS and HPS. Mild cases of HPS can occur.


  • Serologic testing or PCR

HPS is suspected in patients with possible exposure if they have unexplained clinical or radiographic pulmonary edema. Chest x-ray may show increased vascular markings, Kerley B lines, bilateral infiltrates, or pleural effusions. If HPS is suspected, echocardiography should be done to exclude cardiogenic pulmonary edema. CBC, liver function tests, and urinalysis are also usually done. HPS causes mild neutrophilic leukocytosis, hemoconcentration, and thrombocytopenia. Modest elevation of LDH, AST, and ALT, with decreased serum albumin, is typical. Urinalysis shows minimal abnormalities.

Diagnosis is with serologic testing or reverse transcriptase–PCR.


Patients who survive the first few days improve rapidly and recover completely over 2 to 3 wk, often without sequelae. Mortality averages 36%.


  • Supportive care

Treatment is supportive. Mechanical ventilation, meticulous volume control, and vasopressors may be required. For severe cardiopulmonary insufficiency, extracorporal mechanical oxygenation may be lifesaving. IV ribavirin is ineffective.

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