Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 32-04: Viral Hemorrhagic Fevers + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Transmitted by rodents and cause two clinical syndromes Hemorrhagic fever with renal syndrome (HFRS): mild to severe illness Hantavirus pulmonary syndrome (HPS): 40% mortality rate +++ General Considerations ++ Hantaviruses are enveloped RNA bunyaviruses; hosts are rodents, moles, and shrews Hantavirus infection in humans can cause several disease syndromes HFRS caused by Old World hantaviruses Dobrava-Belgrade virus Puumala virus Seoul virus and Hantaan virus in Asia and Europe; these viruses are called Old World hantaviruses Nephropathia epidemica (NE) is a milder form of HFRS. Puumala virus is the most prevalent pathogen and is present throughout Europe. HPS, also known as hantavirus cardiopulmonary syndrome, is caused mainly by Sin Nombre virus and Andes virus, the New World Hantaviruses in Americas A specific strain is not associated with a specific syndrome and overlap is seen between the syndromes Aerosols of virus-contaminated rodent urine and feces are thought to be the main vehicle for transmission to humans Person-to-person transmission is observed only with the Andes virus Occupation at highest risk for transmission of all hantaviruses include Animal trappers Forestry workers Laboratory personnel Farmers Military personnel +++ Demographics ++ A total of 728 cases of hantavirus infection have been reported in the United States since 1993 Average case fatality rate of 36% Most of the cases were reported from states west of the Mississippi River Outbreaks of HPS associated with other hantavirus types are also reported in Central and South America as well as the Caribbean + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Vascular leakage is the hallmark of the disease for both syndromes Kidneys are main target with variants associated with HFRS Lungs are the main target with variants associated with HPS HFRS manifests as mild, moderate, or severe illness depending on the causative strain A 2- to 3-week incubation period is followed by a protracted clinical course, typically consisting of five distinct phases Febrile period Hypotension Oliguria Diuresis Convalescence phase Various degrees of renal involvement are usually seen Puumala virus infection is often referred to as nephropathia epidemica The kidney dysfunction component appears to correlate with levels of the plasma adipokine resistin that may by internalized or diffuse (as a capillary leak syndrome) and often confused with the complications of disseminated intravascular coagulation Thromboembolic phenomena are also recognized complications A secondary hemophagocytic lymphohistiocytosis can be seen with HFRS Pulmonary edema is not typically seen but when present usually occurs in the final stages of disease (oliguric and diuretic phase) Encephalitis and pituitary involvement are rare, although a few cases are reported with Puumala virus Patients may have persistent hematuria, proteinuria, or hypertension up to 35 months after infection Smoking appears to exacerbate the viremia with the Puumula virus infection, and bradycardia can also be prominent Clinical course of HPS is divided into a febrile prodrome, a cardiopulmonary stage, oliguric and diuretic phase followed by convalescence A 14- to 17-day incubation period is followed by a prodromal phase Typically lasts 3–6 days Associated with myalgia, malaise, abdominal pain along with nausea, vomiting, and diarrhea, headache, chills, and fever of abrupt onset Cardiopulmonary phase is characterized by Acute onset of pulmonary edema Cough is generally present Abdominal pain and symptoms as above may dominate the clinical presentation, and in severe cases, significant myocardial depression occurs Acute kidney injury and myositis may occur Sequelae include neuropsychological impairments in some HPS survivors +++ Differential Diagnosis ++ Scrub typhus Leptospirosis Dengue Coxsackievirus Other respiratory infections caused by such pathogens as Legionella, Chlamydia, and Mycoplasma + Diagnosis Download Section PDF Listen +++ ++ Hemoconcentration and elevation in lactate dehydrogenase, serum lactate, and hepatocellular enzymes Early thrombocytopenia and leukocytosis (as high as 90,000 cells/mcL in HPS) are seen in both HFRS and HPS In HPS, immunoblasts (activated lymphocytes with plasmacytoid features) can be seen in blood, lungs, kidneys, bone marrow, liver, and spleen An indirect fluorescent assay and enzyme immunoassay are available for detection of specific IgM or low-avidity IgG virus-specific antibodies A quantitative RT-PCR is available; however, the viremia of human hantavirus infections is short-term and, therefore, viral RNA cannot be readily detected in the blood or urine of patients unless for the more readily detected early viremia of the Andes variant Plaque reduction neutralization test Remains a gold standard serologic assay Distinguishes between the different hantavirus species, although cross reaction between Old and New World viruses exist Needs to be performed in a laboratory with appropriate biosafety (level 3) + Treatment Download Section PDF Listen +++ ++ Supportive Cardiorespiratory support with vasopressors is frequently needed Extracorporeal membrane oxygenation may be required in severe cases of HPS Intravenous ribavirin Used in HFRS (Hantaan virus) with some success in decreasing the severity of the kidney injury Its effectiveness in HPS, however, is not established + Outcome Download Section PDF Listen +++ +++ Prevention ++ Eradication of rodents in houses and avoidance of exposure to rodent excreta, including forest service facilities There is currently no commercially available vaccine and the WHO does not recommend preventive vaccination +++ Prognosis ++ The outcome is highly variable depending on severity of disease HPS is a more severe disease than HFRS, with a mortality rate of about 40% In Sin Nombre virus infections, the persistence of elevated IgG titers correlates with a favorable outcome + References Download Section PDF Listen +++ + +de St Maurice A et al. Exposure characteristics of hantavirus pulmonary syndrome patients, United States, 1993–2015. Emerg Infect Dis. 2017 May;23(5):733–9. [PubMed: 28418312] + +Jangra RK et al. Protocadherin-1 is essential for cell entry by New World hantaviruses. Nature. 2018 Nov;563(7732):559–63. [PubMed: 30464266] + +Jiang H et al. Hantavirus infection: a global zoonotic challenge. Virol Sin. 2017 Feb;32(1):32–43. [PubMed: 28120221] + +Mantula PS et al. High plasma resistin associates with severe acute kidney injury in Puumala hantavirus infection. PLoS One. 2018 Dec 5;13(12):e0208017. [PubMed: 30517161] + +Noh JY et al. Hemorrhagic fever with renal syndrome. Infect Chemother. 2019 Dec;51(4):405–13. [PubMed: 31668027] + +Szabó R. Antiviral therapy and prevention against hantavirus infections. Acta Virol. 2017;61(1):3–12. [PubMed: 28105849] + +Tian H et al. The ecological dynamics of hantavirus diseases: from environmental variability to disease prevention largely based on data from China. PLoS Negl Trop Dis. 2019 Feb 21;13(2):e0006901. [PubMed: 30789905]