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 in North America are Sin Nombre, Black Creek Canal, Bayou, Choclo in Panama, Andes in Argentina, Chile, eastern Bolivia, and Leguna Negra in Bolivia (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 or, rarely through rodent bites. Recent evidence suggests human-to-human transmission may occur with Andes virus. Naturally and laboratory-acquired infections are becoming more common.
Laboratory diagnosis of hantavirus infection is established by serologic tests and reverse transcriptase–polymerase chain reaction (RT-PCR). Serologic tests include enzyme-linked immunosorbent assay (ELISA) and Western and strip immunoblot assays. Serologic diagnosis in North America must be able to differentiate between Seoul and Sin Nombre virus infections due to potential cross-reactivity. Growth of the virus is technically difficult and requires a biosafety level 3 laboratory.
- 1. Milholland MT, Castro-Arellano I, Suzán G, et al: Global diversity and distribution of hantaviruses and their hosts. EcoHealth 15 (1):163-208, 2018. doi:10.1007/s10393-017-1305-2.
Hemorrhagic Fever With Renal Syndrome
(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 polymerase chain reaction (PCR). Mortality is 6 to 15%. Treatment includes IV ribavirin.
Some forms of hemorrhagic fever with renal syndrome are mild (eg, nephropathia epidemica, caused by Puumala virus, as occurs in Scandinavia, the western part of the former Soviet Union, and Europe). Some are usually mild but occasionally may be severe (eg, Seoul virus that has world-wide distribution in wild brown and domesticated rats). Others are severe (eg, that caused by Hantaan virus, as occurs in Korea, China, and Russia, or by Dobrava virus, as occurs in the Balkans).
Infection is transmitted to humans via inhalation of rodent excreta.
Symptoms and Signs
Incubation is about 2 weeks.
In mild forms, infection is often asymptomatic.
When symptoms of HFRS occur, onset is sudden, with high fever, headache, backache, and abdominal pain.
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 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; renal failure may occur.
- Serologic testing or polymerase chain reaction (PCR)
Hemorrhagic fever with renal syndrome is suspected in patients with possible exposure if they have fever, a bleeding tendency, and renal failure.
Complete blood count, 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 red blood cell and white blood cell 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 weeks but may take up to 6 months.
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.
- Sometimes renal dialysis
Treatment of hemorrhagic fever with renal syndrome is with IV ribavirin: loading dose 33 mg/kg (maximum, 2.64 g), followed by 16 mg/kg every 6 hours (maximum, 1.28 g every 6 hours) for 4 days, then 8 mg/kg every 8 hours (maximum, 0.64 g every 8 hours) for 3 days.
Supportive care, which may include renal dialysis, is critical, particularly during the diuretic phase.
Hantavirus Pulmonary Syndrome
Hantavirus pulmonary syndrome (HPS) occurs in the US, primarily in the southwestern states, Canada, primarily in western provinces, and in South America and Panama. It begins as a flu-like illness and, within days, causes noncardiogenic pulmonary edema. Diagnosis is with serologic tests and reverse transcriptase–polymerase chain reaction (RT-PCR). The more severe forms have a case fatality rate of up to 50%. Treatment is supportive.
Most cases of HPS are caused by
- The Sin Nombre (Four Corners virus, Muerto Canyon virus), Andes, and Choclo hantaviruses
Others are caused by
- The Black Creek Canal virus, Muleshoe virus, and Bayou virus in the southeastern US and Mexico
- The New York virus (a variant of Sin Nombre virus) on the East Coast of the US
- The Convict Creek virus and Isla Vista virus on the West Coast of North America
- The Laguna Negra (and its Rio Mamore variant), Andes-like virus Hu39694, Lechiguanas, Oran, Central Plata, Buenos Aires, Rio Mearim, Juquitiba, Juquitiba-like, Ape Aime Itapua, Araucaria, Jabora, Neembucu, Anajatuba, Castelo dos Sonhos, Maripo, and Bermejo hantaviruses in South America
Infection is transmitted to humans via inhalation of excreta of sigmodontine rodents (especially the deer mouse for Sin Nombre virus). Most cases occur west of the Mississippi River in spring or summer, typically after heavy rains that elicit vegetation growth that serves as food that promotes rodent population growth.
Symptoms and Signs
Hantavirus pulmonary syndrome begins as a nonspecific flu-like illness, with acute fever, myalgia, headache, and gastrointestinal 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 polymerase chain reaction (PCR)
Hantavirus pulmonary syndrome 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.
Complete blood count, liver tests, and urinalysis are also usually done. HPS causes mild neutrophilic leukocytosis, hemoconcentration, and thrombocytopenia. Modest elevation of lactic dehydrogenase, aspartate aminotransferase, and alanine aminotransferase, with decreased serum albumin, is typical. Urinalysis shows minimal abnormalities.
Diagnosis of HPS is with serologic testing or reverse transcriptase–PCR.
Patients with HPS who survive the first few days improve rapidly and recover completely over 2 to 3 weeks, often without sequelae. The more severe forms of HPS have a case fatality rate of up to 50%.
- Supportive care
Treatment of hantavirus pulmonary syndrome is supportive. Mechanical ventilation, meticulous volume control, and vasopressors may be required. For severe cardiopulmonary insufficiency, extracorporal mechanical oxygenation may be lifesaving (see also Centers for Disease Control and Prevention: Hantavirus Virus: Treatment) .
Intravenous ribavirin has not been shown to be effective for treatment of HPS despite its effectiveness in hemorrhagic fever with renal syndrome.
- Centers for Disease Control and Prevention: Hantavirus Virus: Information for Health Care Workers
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