- Overview of Arbovirus, Arenavirus, and Filovirus Infections
- Chikungunya Disease
- Dengue
- Dengue Hemorrhagic Fever/Dengue Shock Syndrome
- Hantavirus Infection
- Lassa Fever
- Lymphocytic Choriomeningitis
- Marburg and Ebola Virus Infections
- West Nile Virus
- Yellow Fever
- Zika Virus (ZV) Infections
- Other Arbovirus Infections
Hemorrhagic fever with renal syndrome (HFRS) is a group of similar illnesses caused by hantaviruses, which includes epidemic hemorrhagic fever, Korean hemorrhagic fever, and nephropathia epidemica; these begin 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.Hemorrhagic fever with renal syndrome (HFRS) is a group of similar illnesses caused by hantaviruses, which includes epidemic hemorrhagic fever, Korean hemorrhagic fever, and nephropathia epidemica; these begin 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.
Hantaviridae are a family of enveloped single-stranded RNA viruses, which consists of at least 4 serotypes with 9 viruses causing 2 major, sometimes overlapping, clinical syndromes:
(See also Overview of Arbovirus, Arenavirus, and Filovirus Infections.)
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. Transmission occurs between rodents. Transmission to humans is through inhalation of aerosols of rodent excreta or, rarely through rodent bites. Human-to-human transmission can 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.
General reference
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
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 [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.
In mild forms, infection is often asymptomatic.
Symptomatic HFRS progresses through five phases: febrile, hypotensive, oliguric, polyuric, and convalescent (1).
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% (2). Hemorrhagic complications due to thrombocytopenia may develop (eg, gastrointestinal bleeding, hematuria).
Renal failure develops and patients become oliguric; this phase has the highest risk of mortality. Polyuria then develops and renal function improves.
Symptoms and signs references
1. 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
2. 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 renal failure.
Complete blood count, electrolyte levels, renal function tests, coagulation tests, and urinalysis are then done. Presumptive diagnosis of a hantaviral infection can be quickly confirmed by demonstrating the combination of thrombocytopenia, 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 2nd and 5th day. During the diuretic phase, electrolyte abnormalities are common.
Diagnosis of HFRS is ultimately 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 diuretic phase.
Prognosis for HFRS
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 5 to 15%, almost always occurring in patients with the more severe forms (see Centers for Disease Control and Prevention [CDC]: Hemorrhagic Fever with Renal Syndrome). Residual renal dysfunction is uncommon except in the severe form that occurs in the Balkans.
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 that elicit vegetation growth that serves as food that promotes rodent population growth.
Symptoms and Signs of HPS
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.
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 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.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.
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 (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 Intravenous ribavirin has not been shown to be effective for treatment of HPS despite its effectiveness inhemorrhagic fever with renal syndrome .
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. The more severe forms of HPS have a case fatality rate of up to 50%.
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Centers for Disease Control and Prevention: Hantavirus Virus: Information for Health Care Workers: Information about surveillance case definitions and specimen submission
