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Hantavirus Infection

ByStefania Carmona, MD, University of Alabama at Birmingham
Reviewed ByChristina A. Muzny, MD, MSPH, Division of Infectious Diseases, University of Alabama at Birmingham
Reviewed/Revised Modified Aug 2025
v1020866
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Hantaviridae are a family of enveloped single-stranded RNA viruses. There are over 50 hantavirus species, causing 2 major, sometimes overlapping, clinical syndromes:

Viruses causing HFRS are Hantaan, Seoul, Dobrava (Belgrade), Saaremaa, Amur, and Puumala.

Viruses causing HPS vary by region (1):

  • Argentina: Andes, Araraquara, Bermejo, Juquitiba, Lechiguanas, Leguna Negra, Maciel, and Oran virus

  • Brazil: Araraquara and Juquitiba virus

  • Chile and eastern Bolivia: Andes virus

  • North America: Sin Nombre, Black Creek Canal, Bayou, and Monongahela virus

  • Panama: Choclo virus

  • Paraguay and Bolivia: Leguna Negra virus

Hantaviruses occur throughout the world in wild rodents, which shed the virus throughout life in saliva, urine, and feces (2). Bats, moles, shrews, reptiles, and fish have also been shown to carry hantaviruses. Transmission to humans has only been documented from rodents through inhalation of aerosols of rodent excreta or, rarely through rodent bites. Human-to-human transmission can occur with Andes virus. In addition to naturally acquired infections, laboratory-acquired infections and those occurring without clear exposure to excreta of infected animals 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.

General references

  1. 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.

  2. 2. Vial PA, Ferrés M, Vial C, et al: Hantavirus in humans: a review of clinical aspects and management. Lancet Infect Dis 23(9):e371-e382, 2023. doi:10.1016/S1473-3099(23)00128-7

Hemorrhagic Fever With Renal Syndrome

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 Russia , 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 [Belgrade] virus, as occurs in the Balkans).

Infection is transmitted to humans via inhalation of rodent excreta.

Symptoms and Signs of HFRS

Incubation is about 2 weeks but can be a long as 6 weeks (1).

In mild forms, infection is often asymptomatic.

Symptomatic HFRS progresses through 5 phases: febrile, hypotensive, oliguric, polyuric, and convalescent (2).

The febrile phase has a sudden onset, with high fever, headache, backache, nausea, vomiting, and abdominal pain.

Relative bradycardia is present, and hypotension occurs in about 11 to 40% of febrile patients, with shock in about one-third. Seizures or severe focal neurologic symptoms occur in 1% (3). Hemorrhagic complications due to thrombocytopenia may develop (eg, epistaxis, petechiae, gastrointestinal bleeding, hematuria).

Thrombocytopenia may occur early, even before cardiac symptoms, and the degree of thrombocytopenia is associated with risk of systemic inflammation and development of severe acute kidney injury (1). The oliguric phase is associated with the highest risk of mortality; oliguria is followed by polyuria and improvement in renal function.

Symptoms and signs references

  1. 1. Vial PA, Ferrés M, Vial C, et al: Hantavirus in humans: a review of clinical aspects and management. Lancet Infect Dis 23(9):e371-e382, 2023. doi:10.1016/S1473-3099(23)00128-7

  2. 2. Sehgal A, Mehta S, Sahay K, et al: Hemorrhagic Fever with Renal Syndrome in Asia: History, Pathogenesis, Diagnosis, Treatment, and Prevention. Viruses 15(2):561, 2023. Published 2023 Feb 18. doi:10.3390/v15020561

  3. 3. Lupuşoru G, Lupuşoru M, Ailincăi I, et al: Hanta hemorrhagic fever with renal syndrome: A pathology in whose diagnosis kidney biopsy plays a major role (Review). Exp Ther Med 22(3):984, 2021. doi:10.3892/etm.2021.10416

Diagnosis of HFRS

  • 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 kidney failure.

Initial diagnostic testing includes complete blood count, electrolyte levels, renal function tests, coagulation tests, and urinalysis.. A presumptive diagnosis of a hantavirus infection is based on the presence of thrombocytopenia, decreased plasma albumin, proteinuria, and microhematuria. During the hypotensive phase, hematocrit increases and leukocytosis and thrombocytopenia develop. Albuminuria, hematuria, and red blood cell and white blood cell casts may develop, usually between the second and fifth day. Electrolyte abnormalities are common during the polyuric phase.

A definitive diagnosis of HFRS is based on serologic testing or PCR.

Treatment of HFRS

  • RibavirinRibavirin

  • Sometimes renal dialysis

Treatment of hemorrhagic fever with renal syndrome is with IV ribavirin.Treatment of hemorrhagic fever with renal syndrome is with IV ribavirin.

Supportive care, which may include renal dialysis, is critical, particularly during the polyuric phase.

Prognosis for HFRS

Death can occur during the polyuric 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 1 to 15%, almost always occurring in patients with the more severe forms (1). Residual renal dysfunction is uncommon except in the severe form that occurs in the Balkans.

Prognosis reference

  1. 1. Centers for Disease Control and Prevention: Hantavirus: Clinician Brief: Hemorrhagic Fever with Renal Syndrome. May 20, 2024. Accessed June 17, 2025.

Hantavirus Pulmonary Syndrome

Most cases of HPS are caused by:

  • The Sin Nombre, Andes, and Choclo hantaviruses

Others are caused by:

  • The Black Creek Canal virus, Muleshoe virus, and Bayou virus in the southeastern United States and Mexico

  • The New York virus (a variant of Sin Nombre virus) on the East Coast of the United States

  • 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 causing increased vegetation and promoting rodent population growth.

Symptoms and Signs of HPS

Hantavirus pulmonary syndrome begins as a nonspecific flu-like illness, with acute fever, myalgia, headache, conjunctival injection, retro-ocular pain, and gastrointestinal symptoms. Two to 15 days later (median 4 days), patients rapidly develop noncardiogenic pulmonary edema and hypotension.

As with HFRS, thrombocytopenia may occur early, even before cardiopulmonary symptoms, and the degree of thrombocytopenia is associated with risk of systemic inflammation and development of severe acute kidney injury (1).

Several patients have had a combination of HFRS and HPS. Mild cases of HPS can occur.

Symptoms and signs reference

  1. 1. Vial PA, Ferrés M, Vial C, et al. Hantavirus in humans: a review of clinical aspects and management. Lancet Infect Dis 2023;23(9):e371-e382. doi:10.1016/S1473-3099(23)00128-7

Diagnosis of HPS

  • 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 radiograph 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.

Initial tests include complete blood count, liver biochemical tests, electrolyte and renal function blood studies as well as urinalysis. 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.

Treatment of HPS

  • 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 (1).

Intravenous ribavirin has not been shown to be effective for treatment of HPS despite its effectiveness in Intravenous ribavirin has not been shown to be effective for treatment of HPS despite its effectiveness inhemorrhagic fever with renal syndrome .

Treatment reference

  1. 1. Centers for Disease Control and Prevention: Hantavirus: Clinician Brief: Hantavirus Pulmonary Syndrome (HPS). May 23, 2024. Accessed June 17, 2025.

Prognosis for HPS

Patients with HPS who survive the first few days improve rapidly and recover completely over 2 to 3 weeks, often without sequelae. However, without early treatment, HPS fatality rate is nearly 40% (1).

Prognosis reference

  1. Centers for Disease Control and Prevention: Hantavirus: Clinician Brief: Hantavirus Pulmonary Syndrome (HPS). May 23, 2024. Accessed June 17, 2025.

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