Hantavirus infection overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Basir Gill, M.B.B.S, M.D.[2] Usama Talib, BSc, MD [3]
Overview
Hantavirus infection is a zoonotic disease caused by viruses of the genus Orthohantavirus, family Hantaviridae, order Bunyavirales.[1] Hantaviruses are enveloped, negative-sense, single-stranded RNA viruses with a tripartite genome (small [S], medium [M], and large [L] segments) and are approximately 80–120 nm in diameter.[2] Approximately 150,000–200,000 cases of hantavirus disease are reported worldwide each year.[2][3]
Hantaviruses cause two major clinical syndromes: hemorrhagic fever with renal syndrome (HFRS), endemic in Europe and Asia, and hantavirus cardiopulmonary syndrome (HCPS), endemic in the Americas.[2] A milder form of HFRS caused by Puumala virus is termed nephropathia epidemica (NE).[4] Although HFRS and HCPS are recognized as distinct clinical entities, they share overlapping symptoms, signs, and pathogenic alterations, and both can involve the kidneys and lungs.[2]
Transmission to humans occurs primarily via inhalation of aerosolized viral particles shed in rodent urine, feces, and saliva, and rarely by rodent bites.[2] Andes virus (ANDV) is unique among hantaviruses in that it can be transmitted from person to person.[5]
Endothelial cells of capillaries and small vessels are the principal targets of hantaviruses, and increased vascular permeability is central to pathogenesis.[2] Diagnosis is primarily serological (IgM ELISA), supplemented by RT-qPCR and clinical algorithms.[2] There is no specific approved antiviral treatment or vaccine in Europe or the Americas; treatment is primarily supportive, with extracorporeal membrane oxygenation (ECMO) for severe HCPS.[2][6]
The case fatality rate (CFR) varies by virus: HCPS caused by Sin Nombre virus (SNV) or ANDV carries a CFR of 30–45%, while HFRS caused by Hantaan virus (HTNV) or Dobrava virus (DOBV) has a CFR of 5–15%, and PUUV-associated NE has a CFR of less than 1%.[2][7]
Historical Perspective
Ancient and early descriptions: HFRS was first clinically recognized in northeast China in 1931.[8] A similar illness, termed "Korean hemorrhagic fever," was recognized among United Nations troops during the Korean War in the 1950s, with a case fatality rate of 5–7%.[2]
Discovery of Hantaan virus: In 1976, Ho Wang Lee isolated the first pathogenic hantavirus from the lungs of the striped field mouse (Apodemus agrarius) near the Hantaan River in South Korea. The virus was named Hantaan virus (HTNV) in 1978.[8][2] Subsequently, several other hantaviruses were identified throughout Europe and Asia, including Puumala virus, Dobrava virus, and Seoul virus.[2]
Discovery of HCPS and Sin Nombre virus: In May 1993, a cluster of unexplained deaths from acute respiratory failure was identified in the Four Corners region of the southwestern United States. The initial 17 patients presented with rapidly progressive respiratory and hemodynamic deterioration, with a case fatality rate of 76%.[9] A genetically distinct hantavirus was identified as the causative agent and later named Sin Nombre virus (SNV), with the deer mouse (Peromyscus maniculatus) as its reservoir.[2][10]
Person-to-person transmission: In 1996, the first documented person-to-person transmission of a hantavirus (ANDV) occurred during an outbreak in El Bolsón, Argentina, involving 16 epidemiologically linked cases.[11] Since then, many HCPS-causing hantaviruses have been identified throughout the Americas.[2]
Classification
Hantavirus infection can be classified based on the causative virus species and the resulting clinical syndrome.[4]
By Clinical Syndrome
| Clinical Syndrome | Geographic Distribution | Primary Viruses | Rodent Reservoir | Case Fatality Rate |
|---|---|---|---|---|
| Hemorrhagic fever with renal syndrome (HFRS) | Europe, Asia | Hantaan virus (HTNV), Dobrava virus (DOBV), Seoul virus (SEOV) | Apodemus agrarius, Apodemus flavicollis, Rattus norvegicus | 1–15% |
| Nephropathia epidemica (NE) (mild HFRS) | Europe (Finland, Germany, Sweden, Russia) | Puumala virus (PUUV) | Myodes glareolus (bank vole) | 1% |
| Hantavirus cardiopulmonary syndrome (HCPS) | Americas | Sin Nombre virus (SNV), Andes virus (ANDV), Choclo virus (CHOV), Laguna Negra virus (LANV) | Peromyscus maniculatus, Oligoryzomys longicaudatus | 12–45% |
By Virus Taxonomy
Hantaviruses belong to the genus Orthohantavirus, family Hantaviridae, order Bunyavirales.[1] The family Hantaviridae contains viruses with genomes of approximately 10.5–14.6 kb, maintained in and/or transmitted by fish, reptiles, and mammals.[1] Over 50 species have been described, of which more than 24 are recognized as pathogenic to humans.[12]
Old World hantaviruses (HFRS-causing): HTNV, DOBV, PUUV, SEOV, Tula virus
New World hantaviruses (HCPS-causing): SNV, ANDV, Araraquara virus, Juquitiba virus, CHOV, LANV, Black Creek Canal virus, Bayou virus
Causes
Hantaviruses are RNA viruses of the genus Orthohantavirus, family Hantaviridae, order Bunyavirales.[1] Each is made up of negative-sensed, single-stranded RNA viruses. Each viral particle is enveloped, 80–120 nm in diameter, and contains a genome with three segments:[2][12]
Small (S) segment: encodes the nucleocapsid protein (N), and in some hantaviruses, a non-structural protein (NSs)
Medium (M) segment: encodes the glycoprotein precursor (GPC), which is cleaved into envelope glycoproteins Gn and Gc
Large (L) segment: encodes the RNA-dependent RNA polymerase (RdRp)
There are 5 genera within the order Bunyavirales that historically comprised the former family bunyaviridae: bunyavirus, phlebovirus, nairovirus, tospovirus, and hantavirus. All these genera include arthropod-borne viruses, with the exception of hantavirus, which is a genus of rodent-borne agents.
Rodents are the main natural hosts for pathogenic hantaviruses, although bats, moles, shrews, reptiles, and fish have also been shown to carry hantaviruses.[2] Natural hosts are believed to be persistently infected with little biological effect. Rodents excrete hantaviruses in saliva, urine, and feces, and humans are infected primarily when inhaling aerosolized secreted viruses, or rarely by rodent bites.[2] Dynamics of rodent populations and factors such as rainfall, temperature, land use, habitat changes, social development, and human behavior influence the interaction between rodent hosts and humans.[2]
Data on environmental viability are limited. Puumala virus remained infectious for up to 15 days in bank vole bedding and remained viable at room temperature for 5 days in a wet environment and 24 hours when dry. HTNV survived in wet conditions for 8 days at 20°C and 9 days at 37°C.[2]
Differentiating Hantavirus Infection from Other Diseases
Hantavirus infection must be differentiated from other diseases that present with hemorrhagic fever, acute respiratory distress syndrome, or acute kidney injury. Hemorrhagic fever caused by hantavirus can be differentiated from other diseases such as dengue, malaria and Ebola. The hantavirus cardiopulmonary syndrome can be differentiated from other diseases like histoplasmosis, coccidioidomycosis, brucellosis, tuberculosis and aspergillosis.[2]
| Disease | Key Differentiating Features |
|---|---|
| Leptospirosis | Conjunctival suffusion, jaundice, exposure to contaminated water; positive Leptospira serology or PCR |
| Dengue | Rash, retro-orbital pain, leukopenia; positive dengue NS1 antigen or serology; tropical/subtropical travel |
| Malaria | Cyclical fever, splenomegaly, anemia; positive blood smear or rapid diagnostic test; travel to endemic area |
| Ebola virus disease | Severe hemorrhage, diarrhea, contact with infected individuals; positive Ebola PCR; sub-Saharan Africa exposure |
| Pneumonic plague | Rapidly progressive pneumonia, hemoptysis, lymphadenopathy; gram-negative bipolar rods; southwestern US exposure |
| Influenza | Rhinorrhea, pharyngitis, seasonal pattern; positive influenza rapid antigen or PCR |
| Histoplasmosis | Chronic cough, mediastinal lymphadenopathy, hepatosplenomegaly; positive urine/serum Histoplasma antigen |
| Coccidioidomycosis | Erythema nodosum, arthralgia, southwestern US exposure; positive Coccidioides serology |
| Tuberculosis | Chronic cough, night sweats, weight loss, upper lobe infiltrates; positive AFB smear/culture or PCR |
| Aspergillosis | Immunocompromised host, halo sign on CT, hemoptysis; positive galactomannan or culture |
| Brucellosis | Undulant fever, sacroiliitis, hepatosplenomegaly, animal exposure; positive Brucella serology or culture |
| Rickettsiosis | Eschar, rash, tick exposure; positive rickettsial serology |
| Crimean-Congo hemorrhagic fever | Severe hemorrhage, tick exposure; positive CCHF PCR; endemic regions (Africa, Asia, southeastern Europe) |
| HELLP syndrome (in pregnancy) | Hypertension, proteinuria, elevated liver enzymes, hemolysis, low platelets; third trimester |
| Community-acquired pneumonia | Productive cough, focal consolidation, leukocytosis with toxic granulation; positive sputum culture |
Key distinguishing features of HCPS include the combination of thrombocytopenia, hemoconcentration, leukocytosis with a left shift but without toxic granulation, and the presence of circulating immunoblasts on peripheral blood smear.[2][9]
Pathophysiology
Hantavirus is usually transmitted via the inhalation of aerosolized viral antigens or rodent bites. The incubation period of hantavirus infection is 9 to 33 days, though ranges of 7 to 39 days in HCPS and 14 to 28 days in HFRS have been reported.[12][2]
Cellular Targets and Vascular Permeability
Following inhalation, the virus replicates in pulmonary macrophages and dendritic cells before disseminating to endothelial cells.[12] The primary target cells of hantavirus infection are endothelial cells of capillaries and small vessels.[2] Increased vascular permeability is central to pathogenesis and does not appear to be caused by a lytic effect of the virus, but rather by functional changes of the endothelial barrier through mechanisms that remain incompletely understood.[2] These mechanisms include:
Binding of the virus to cell receptors (including β3 integrins) that regulate endothelial permeability
Increased innate immune responses and immunopathogenic mechanisms
Overexpression of vascular endothelial growth factor (VEGF), which promotes degradation of VE-cadherin and disrupts intercellular contacts[12]
Activation of the plasma kallikrein-kinin system, leading to increased cleavage of high molecular weight kininogen, liberation of bradykinin, and dramatic increases in endothelial cell permeability[13]
Infection is followed by impairment of the barrier function of endothelial cells, fluid extravasation, and subsequent organ failure.[4]
Immune Response
The immune response plays a central role in hantavirus pathogenesis:[12]
Elevated CD8+ T cell responses correlate with disease severity and systemic organ dysfunction
T regulatory cell (Treg) responses are downregulated during human infection, in contrast to the upregulated Treg response that promotes viral persistence in rodent hosts
A "cytokine storm" involving IL-6, IL-1β, TNF, and other pro-inflammatory cytokines contributes to endothelial dysfunction
Genetic vulnerability due to certain human leukocyte antigen (HLA) haplotypes is associated with disease severity[6]
Organ Tropism
Endothelial cells in the lungs, kidneys, heart, liver, and spleen can be infected, as can macrophages, mononuclear blood cells, dendritic cells, and respiratory and tubular epithelium.[2] According to histopathological studies:
HFRS-causing hantaviruses primarily affect renal medullary capillaries
HCPS-causing hantaviruses mainly affect pulmonary capillaries[2][6]
In HFRS, endothelial activation leads to platelet activation and altered coagulation. Kidney biopsies show interstitial hemorrhage, microvascular inflammation with T cells and macrophages, and peritubular capillaritis.[2]
Epidemiology and Demographics
Hantavirus infection has a diverse epidemiology and demographics due to the vast number of viruses classified under hantaviruses. Approximately 150,000–200,000 cases of hantavirus disease are reported worldwide each year, with the majority occurring in China.[2][3]
HFRS: China reports 20,000–50,000 cases annually, accounting for the majority of global HFRS cases. In Europe, Finland reports the highest incidence of PUUV-associated nephropathia epidemica, with up to 3,000 cases per year. Germany, Sweden, and Russia also report significant numbers. SEOV-associated HFRS occurs worldwide due to the global distribution of Rattus norvegicus.[2][8]
HCPS: The total number of hantavirus pulmonary syndrome (HPS) cases reported in the United States from 2004–2015 is 323. HPS cases have been reported in 30 states, including most of the western half of the country and some eastern states as well. Over half of the confirmed cases have been reported from areas outside the Four Corners area. The mean age of confirmed HPS cases is 38 years (range: 5 to 84 years).[14] In South America, Argentina, Chile, Brazil, and Panama report the highest numbers of HCPS cases. Argentina reports 100–200 cases per year, and Chile reports 50–100 cases per year.[2]
Males are disproportionately affected in both HFRS and HCPS, likely reflecting occupational and recreational exposure patterns. Seasonal peaks correlate with rodent population dynamics: HFRS peaks in autumn and winter in China, while PUUV-associated NE peaks in late autumn in northern Europe. HCPS in the Americas shows spring and summer peaks.[8][2]
Risk Factors
The most potent risk factor in the development of hantavirus infection is exposure to rodent excreta and close contact with hantavirus-infected humans.[8]
Risk factors include:
Peridomestic rodent exposure: Living in or near rodent-infested dwellings, particularly rural or semi-rural settings
Occupational exposure: Forestry workers, farmers, military personnel, and laboratory workers handling rodents or rodent-contaminated materials
Recreational exposure: Camping, hiking, or entering enclosed spaces (cabins, sheds, barns) with rodent infestation
Cleaning activities: Sweeping or vacuuming areas contaminated with rodent droppings, urine, or nesting materials, which aerosolizes viral particles
Climatic and ecological factors: Increased rainfall and mild winters promote rodent population growth and subsequent human exposure[8][2]
Person-to-person contact (ANDV only): Close contact with an ANDV-infected individual, including sexual contact, sleeping in the same room, or providing direct care[11]
Screening
There are no screening recommendations for hantavirus infection.
Diagnosis
History and Symptoms
Hantavirus infection should be suspected in patients who reside in or have recent (5–50 days prior) travel history to an endemic region, presenting with:[2]
Persistent fever (>48 hours), headache, myalgia, and gastrointestinal manifestations (abdominal pain, vomiting, diarrhea)
In more advanced illness: cough, dyspnea, hypoxia, and bilateral pulmonary infiltrates
Acute renal dysfunction
In ANDV-endemic regions: close contact with an infected patient in the previous 40 days, particularly sexual contact or sleeping in the same room[2]
HFRS classically progresses through five stages: febrile, hypotensive, oliguric, diuretic, and convalescent. After an incubation period of 2–6 weeks, prominent features include acute onset of high fever with headache, nausea, myalgia, and abdominal and back pain.[2]
HCPS begins with a febrile prodrome (2–7 days) of myalgia, headache, chills, abdominal pain, vomiting, diarrhea, arthralgia, conjunctival injection, and retro-orbital pain. This is followed by the cardiopulmonary phase with sudden onset of cough, dyspnea, tachycardia, and hypotension, progressing within hours to non-cardiogenic pulmonary edema, respiratory failure, and often cardiogenic shock.[2] The cardiopulmonary phase lasts 2–4 days, with most deaths occurring within the first 24 hours after hospital admission.[2]
Physical Examination
Patients with hantavirus infection usually exhibit prostration. Physical examination findings may include:[2][4]
Fever and diaphoresis
Hypotension and signs of shock (mottling, prolonged capillary refill time)
Tachycardia and tachypnea
Petechiae (skin or mucosa; in ANDV, particularly axillae and extremities)
Abdominal tenderness (may mimic acute abdomen)
Epistaxis, menorrhagia, or gastrointestinal bleeding (more common in severe HFRS caused by HTNV and DOBV)
Bilateral crackles on lung auscultation
Low blood pressure and abnormal cardiopulmonary examination[4]
Laboratory Findings
Serological Testing
ELISA for IgM antibodies directed against hantavirus nucleocapsid protein is the most widely used diagnostic test. IgM antibodies are often present at onset of the febrile prodrome, and IgG antibodies are usually present by the end of the febrile prodrome.[2] Immunochromatographic IgM assays have assay performance greater than 90% compared with EIA IgM assays.[2]
Evidence of viral antigen in tissue by immunohistochemistry, or the presence of amplifiable viral RNA sequences in blood or tissue, with a compatible history of HPS, is considered diagnostic for HPS.[2]
Molecular Testing
RT-qPCR, usually designed to detect the S segment, is sensitive and specific. Viral loads are higher in buffy coat than in plasma. RT-qPCR can detect ANDV RNA for up to 2 weeks before symptom onset and for weeks after resolution of symptoms.[2][5]
Presumptive Diagnosis (HCPS)
In the cardiopulmonary phase, a presumptive diagnosis can be established using blood count or peripheral smear criteria. The presence of at least 4 out of 5 criteria has a sensitivity of 96% and a specificity of 99%:[2]
Thrombocytopenia Left shift in the granulocytic lineage Absence of toxic granulation in the myeloid series Hemoconcentration Immunoblast population greater than 10% of the total leukocyte population
Prognostic Laboratory Markers
A platelet count greater than 115,000/μL at admission is associated with lower risk of progression to severe HCPS
A platelet count lower than 40,000/μL is associated with increased mortality
Positive quantitative proteinuria at hospital admission has been linked to mortality[2]
Urine Analysis
Detection of proteinuria and hematuria with urine dipstick analysis supports the clinical suspicion of HFRS.[2]
X ray
On chest X-ray, HCPS may manifest as non-cardiogenic pulmonary edema characterized by bilateral alveolar infiltrates.[2] Radiographic progression from interstitial to alveolar edema may occur rapidly over hours.[9]
CT scan
On CT scan, hantavirus pulmonary syndrome is characterized by ground-glass opacities and interlobular and intralobular septal thickening. Pleural effusions may also be present.[2]
MRI
There are no specific MRI findings associated with hantavirus infection. MRI may occasionally demonstrate pituitary hemorrhage or encephalitis in rare cases of central nervous system involvement.[6]
Ultrasound
On renal ultrasound, hantavirus hemorrhagic fever with renal syndrome may show parenchymal edema, increased echogenicity, and decreased corticomedullary differentiation.[6]
Other Imaging Findings
There are no other specific imaging findings associated with hantavirus infection.
Other Diagnostic Studies
Additional diagnostic findings can include the histopathological analysis of lymph nodes, spleen, and liver, but these are rarely used in clinical practice. Autopsy findings in HCPS typically show heavy, edematous lungs with serous pleural effusions and interstitial pneumonitis with mononuclear cell infiltrates.[10]
Treatment
Initial Management
There is no specific treatment, cure, or vaccine for hantavirus infection. Treatment is primarily supportive. Infected individuals who are recognized early and receive medical care in an intensive care unit may have improved outcomes.[2][15]
HCPS: Early recognition during the febrile prodrome and prompt transfer to a facility with ICU and ECMO capability is critical. Aggressive volume resuscitation should be avoided, as it may worsen pulmonary edema due to the underlying capillary leak. Judicious fluid management guided by hemodynamic monitoring is recommended.[2]
HFRS: Supportive care includes careful fluid and electrolyte management, analgesics for pain, and monitoring for hemorrhagic complications. Hemodialysis may be required in the oliguric phase; approximately 5% of PUUV-HFRS and up to 15% of DOBV-HFRS patients require renal replacement therapy.[2][6]
Medical Therapy
Antiviral Agents
Ribavirin: An open-label trial in China demonstrated reduced mortality in HFRS when ribavirin was administered intravenously within the first 5 days of illness.[2] However, ribavirin has not shown benefit in PUUV-associated HFRS or in HCPS. A randomized controlled trial of intravenous ribavirin for HCPS was terminated early due to futility.[2][7]
Favipiravir: Has shown efficacy in animal models of hantavirus infection when administered before peak viremia, but human clinical trial data are lacking.[7]
Icatibant: A bradykinin B2 receptor antagonist that has been used in individual cases of severe HFRS with reported clinical improvement, based on the role of the kallikrein-kinin system in hantavirus pathogenesis.[2]
Immunotherapy
Convalescent plasma: An open-label study in Chile showed lower mortality in ANDV-associated HCPS patients treated with high-titer neutralizing antibodies from convalescent donors compared with historical controls.[2] A randomized controlled trial was conducted but results remain pending full publication.[2]
Corticosteroids
Methylprednisolone: A randomized, double-blind, placebo-controlled trial of high-dose intravenous methylprednisolone in HCPS showed no benefit in reducing mortality or disease severity.[2]
Hemodynamic Support
Inotropes such as dobutamine or low-dose epinephrine are preferred for hemodynamic support in HCPS-associated cardiogenic shock, rather than aggressive volume resuscitation.[2]
Vasopressors (norepinephrine) may be required for refractory hypotension.[2]
Procedural / Surgical Therapy
Extracorporeal Membrane Oxygenation (ECMO)
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is the most important rescue therapy for severe HCPS with refractory cardiogenic shock. In a retrospective series, survival rates of approximately 70–80% were reported in patients with severe HCPS treated with early VA-ECMO, compared with near-universal mortality without mechanical circulatory support in this population.[16][17]
Indications for ECMO in HCPS include:[17]
Refractory cardiogenic shock despite inotropic support
Cardiac index less than 2.2 L/min/m² with rising lactate
Severe metabolic acidosis unresponsive to medical therapy
Hemodialysis
Hemodialysis or continuous renal replacement therapy may be required in HFRS patients with severe oliguric acute kidney injury.[6]
Surgery
Surgical intervention is not recommended for the management of hantavirus infection. Rare surgical indications may arise from complications such as pituitary hemorrhage or severe hemorrhagic complications requiring intervention.[6]
Long-Term Management
Long-term follow-up is recommended for survivors of both HCPS and HFRS:
Post-HCPS: Persistent fatigue, reduced exercise tolerance, and impaired pulmonary function (reduced diffusing capacity) have been reported for up to 1–3 years after acute illness.[2]
Post-HFRS/NE: Long-term renal follow-up is advisable. A study with up to 20 years of follow-up after nephropathia epidemica found that 8% of patients developed chronic kidney disease (CKD), and hypertension was frequent, although a causal relationship remained uncertain.[18] Hormonal dysfunction, particularly involving the anterior pituitary, has been reported in up to 80% of PUUV patients at follow-up.[6]
Monitoring of renal function, blood pressure, and pituitary hormones is recommended in HFRS/NE survivors.[6][18]
Prevention
Primary Prevention
Prevention of hantavirus infection centers on reducing human exposure to rodents and their excreta.[19]
Indoor Measures
Seal holes and gaps in homes, garages, and outbuildings to prevent rodent entry
Store food in sealed containers and dispose of garbage promptly
Place snap traps in and around the home to decrease rodent infestation
When cleaning areas with evidence of rodent infestation:
Ventilate the area for at least 30 minutes before entering
Do not sweep or vacuum rodent droppings, urine, or nesting materials (this aerosolizes viral particles)
Wet contaminated areas with a 10% bleach solution or commercial disinfectant and allow to soak for 5 minutes before wiping up with damp towels
Wear rubber or latex gloves during cleanup[19]
Outdoor Measures
Eliminate rodent harborage areas (woodpiles, junk, dense vegetation) within 30 meters of the home
Use elevated platforms for camping and avoid sleeping on bare ground in endemic areas
Store food in rodent-proof containers when camping or hiking[19]
Occupational and Recreational Precautions
Workers in high-risk settings (forestry, agriculture, military) should use appropriate personal protective equipment, including respirators (N95 or higher) when cleaning heavily contaminated enclosed spaces
Recent research results show that many people who became ill with HPS developed the disease after having been in frequent contact with rodents and/or their droppings around a home or a workplace. On the other hand, many people who became ill reported that they had not seen rodents or rodent droppings at all. Therefore, if living in an area where the carrier rodents are known to live, efforts should be made to keep the home, vacation place, workplace, or campsite clean.[19]
Person-to-Person Transmission Prevention (Andes Virus)
In ANDV-endemic regions, suspected HCPS patients should be placed in contact isolation and droplet isolation
Household contacts of confirmed ANDV cases should be monitored for symptoms for at least 40 days after last exposure[2][11]
Vaccines
Inactivated hantavirus vaccines (against HTNV and SEOV) have been used in China and South Korea, but clear efficacy data from randomized controlled trials are lacking.[7] No approved vaccine exists in Europe or the Americas. Several vaccine candidates are in preclinical or early clinical development, including DNA vaccines and virus-like particle platforms.[7][12]
Secondary Prevention
Secondary preventive measures for hantavirus infection are similar to primary prevention. Early recognition of symptoms in exposed individuals and prompt medical evaluation may reduce morbidity and mortality. In ANDV-endemic areas, monitoring of close contacts of confirmed cases is essential.[2]
Special Populations
Pregnancy
Hantavirus infection during pregnancy poses risks to both the mother and fetus. Disease severity appears similar for PUUV, DOBV, and ANDV infections in pregnant women compared with non-pregnant adults, although HTNV infection may be more severe in the third trimester.[2] Intrauterine transmission of hantavirus is very rare but has been documented. Transmission via breast milk has also been reported in isolated cases.[2][20] Hantavirus infection in pregnancy may mimic HELLP syndrome or preeclampsia due to overlapping features of thrombocytopenia, elevated liver enzymes, and proteinuria.[2]
Pediatric Population
Hantavirus infection is uncommon in children. In the United States, fewer than 7% of confirmed HPS cases have occurred in patients younger than 17 years, and the disease is rare in children under 10 years of age.[21] Clinical presentation in children may be similar to adults, though data are limited.
Immunocompromised Patients
Data on hantavirus infection in immunocompromised patients are limited. There is no clear evidence that immunosuppression increases susceptibility or severity, although the immune-mediated component of pathogenesis suggests that the clinical course could differ in this population.[6]
Natural History, Complications and Prognosis
Natural History
If left untreated, hantavirus infection may progress to multi-organ failure and death. The natural history varies by syndrome:
HCPS: Progresses from febrile prodrome (2–7 days) to cardiopulmonary phase (2–4 days) with rapid deterioration. Most deaths occur within the first 24 hours after hospital admission. Survivors typically enter a diuretic phase with gradual recovery over weeks to months.[2]
HFRS: Progresses through five phases (febrile, hypotensive, oliguric, diuretic, convalescent) over 2–6 weeks. Recovery may take weeks to months.[2]
Complications
Possible complications of hantavirus infection include:[2][6][22]
Acute respiratory distress syndrome
Pulmonary edema (non-cardiogenic)
Cardiogenic shock and myocardial depression
Acute kidney injury and oliguric renal failure
Disseminated intravascular coagulation
Thrombocytopenia and hemorrhagic complications
Pituitary hemorrhage
Acute encephalomyelitis
Shock and multi-organ failure
Prognosis
The prognosis of hantavirus infection depends on the causative virus and clinical syndrome:
| Syndrome / Virus | Case Fatality Rate |
|---|---|
| HCPS — Sin Nombre virus (SNV) | 30–40% |
| HCPS — Andes virus (ANDV) | 30–45% |
| HCPS — Choclo virus (CHOV), Laguna Negra virus (LANV) | 12–15% |
| HFRS — Hantaan virus (HTNV) | 5–10% |
| HFRS — Dobrava virus (DOBV) | 10–12% |
| HFRS — Seoul virus (SEOV) | 1–2% |
| NE — Puumala virus (PUUV) | 1% |
Early recognition, prompt ICU admission, and availability of ECMO for severe HCPS are associated with improved survival.[2][16][15]
Indications for Referral
All suspected cases of hantavirus infection should be reported to public health authorities, as hantavirus disease is a notifiable disease in most jurisdictions
Patients with suspected HCPS should be transferred urgently to a facility with ICU and ECMO capability[17]
Infectious disease consultation is recommended for all confirmed or suspected cases
Nephrology consultation for HFRS patients with acute kidney injury requiring renal replacement therapy[6]
Pulmonology and critical care consultation for patients with respiratory failure
Endocrinology referral for survivors with suspected pituitary dysfunction[6]
In ANDV-endemic regions, infection control teams should be notified for implementation of isolation precautions and contact tracing[2]
References
- ↑ 1.0 1.1 1.2 1.3 Bradfute SB, Calisher CH, Klempa B, Klingström J, Kuhn JH, Laenen L, Maes P, Radoshitzky SR, Rubbenstroth D, Shi M, Song JW, Yanagihara R (2024). "ICTV Virus Taxonomy Profile: Hantaviridae 2024". J Gen Virol. 105 (4). doi:10.1099/jgv.0.001975. PMID 38587456 Check
|pmid=value (help). - ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 2.25 2.26 2.27 2.28 2.29 2.30 2.31 2.32 2.33 2.34 2.35 2.36 2.37 2.38 2.39 2.40 2.41 2.42 2.43 2.44 2.45 2.46 2.47 2.48 2.49 2.50 2.51 2.52 2.53 2.54 2.55 2.56 2.57 2.58 2.59 2.60 2.61 2.62 2.63 2.64 2.65 2.66 2.67 2.68 Vial PA, Ferrés M, Vial C, Klingström J, Ahlm C, López R, Le Corre N, Mertz GJ (2023). "Hantavirus in humans: a review of clinical aspects and management". Lancet Infect Dis. 23 (9): e371–e382. doi:10.1016/S1473-3099(23)00128-7. PMID 37105214 Check
|pmid=value (help). - ↑ 3.0 3.1 Romeo MA, Tofani S, Lapa D, Castilletti C, Vaia F, Maggi F (2025). "Orthohantaviruses: An Overview of the Current Status of Diagnostics and Surveillance". Viruses. 17 (5): 622. doi:10.3390/v17050622. PMID 40431633 Check
|pmid=value (help). - ↑ 4.0 4.1 4.2 4.3 4.4 Jiang H, Zheng X, Wang L, Du H, Wang P, Bai X (2017). "Hantavirus infection: a global zoonotic challenge". Virol Sin. 32 (1): 32–43. doi:10.1007/s12250-016-3899-x. PMID 28120221.
- ↑ 5.0 5.1 Ferrés M, Martínez-Valdebenito C, Henriquez C, Vial C, Mancilla C, Vial PA (2024). "Viral shedding and viraemia of Andes virus during acute hantavirus infection: a prospective study". Lancet Infect Dis. 24 (7): 775–782. doi:10.1016/S1473-3099(24)00142-7. PMID 38582089 Check
|pmid=value (help). - ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 Koehler FC, Di Cristanziano V, Späth MR, Nörz D, Fischer L, Grundmann F, Pfister H, Lütgehetmann M, Kochanek M, Becker JU, Müller RU (2022). "The kidney in hantavirus infection-epidemiology, virology, pathophysiology, clinical presentation, diagnosis and management". Clin Kidney J. 15 (7): 1231–1252. doi:10.1093/ckj/sfac008. PMID 35756741 Check
|pmid=value (help). - ↑ 7.0 7.1 7.2 7.3 7.4 Liu R, Ma H, Shu J, Zhang Q, Han M, Liu Z, Jin X, Zhang F, Wu X (2019). "Vaccines and Therapeutics Against Hantaviruses". Front Microbiol. 10: 2989. doi:10.3389/fmicb.2019.02989. PMID 32082263 Check
|pmid=value (help). - ↑ 8.0 8.1 8.2 8.3 8.4 8.5 Watson DC, Sargianou M, Papa A, Chra P, Starakis I, Panos G (2014). "Epidemiology of Hantavirus infections in humans: a comprehensive, global overview". Crit Rev Microbiol. 40 (3): 261–72. doi:10.3109/1040841X.2013.783555. PMID 23607444.
- ↑ 9.0 9.1 9.2 Duchin JS, Koster FT, Peters CJ, Simpson GL, Tempest B, Zaki SR, Ksiazek TG, Rollin PE, Nichol S, Umland ET (1994). "Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease. The Hantavirus Study Group". N Engl J Med. 330 (14): 949–55. doi:10.1056/NEJM199404073301401. PMID 8141498.
- ↑ 10.0 10.1 Zaki SR, Greer PW, Coffield LM, Goldsmith CS, Nolte KB, Foucar K, Feddersen RM, Zumwalt RE, Miller GL, Khan AS (1995). "Hantavirus pulmonary syndrome. Pathogenesis of an emerging infectious disease". Am J Pathol. 146 (3): 552–79. PMID 7887439.
- ↑ 11.0 11.1 11.2 Martínez VP, Di Paola N, Alonso DO, Pérez-Sautu U, Bellomo CM, Iglesias AA, Coelho RM, López B, Periolo N, Larson PA, Nagle ER, Chitty JA, Pratt CB, Díaz J, Cisterna D, Campos J, Sharma H, Dighero-Kemp B, Biondo E, Lewis L, Tattoli I, Palacios G (2020). ""Super-Spreaders" and Person-to-Person Transmission of Andes Virus in Argentina". N Engl J Med. 383 (23): 2230–2241. doi:10.1056/NEJMoa2009040. PMID 32553608 Check
|pmid=value (help). - ↑ 12.0 12.1 12.2 12.3 12.4 12.5 12.6 Saavedra F, Díaz FE, Retamal-Díaz A, Bueno SM, Kalergis AM, Gálvez N (2021). "Immune response during hantavirus diseases: implications for immunotherapies and vaccine design". Immunology. 163 (3): 262–277. doi:10.1111/imm.13322. PMID 33751578 Check
|pmid=value (help). Vancouver style error: initials (help) - ↑ Taylor SL, Wahl-Jensen V, Copeland AM, Jahrling PB, Schmaljohn CS (2013). "Endothelial cell permeability during hantavirus infection involves factor XII-dependent increased activation of the kallikrein-kinin system". PLoS Pathog. 9 (7): e1003470. doi:10.1371/journal.ppat.1003470. PMID 23874198.
- ↑ "Hantavirus Pulmonary Syndrome (HPS) Cases, by State of Exposure". Centers for Disease Control and Prevention.
- ↑ 15.0 15.1 Mertz GJ, Hjelle B, Crowley M, Iwamoto G, Tomicic V, Vial PA (2006). "Diagnosis and treatment of new world hantavirus infections". Curr Opin Infect Dis. 19 (5): 437–42. doi:10.1097/01.qco.0000244048.38758.1f. PMID 16940866.
- ↑ 16.0 16.1 Crowley MR, Katz RW, Kessler R, Simpson SQ, Levy H, Hallin GW, Cappon J, Krahling JB, Wernly J (1998). "Successful treatment of adults with severe Hantavirus pulmonary syndrome with extracorporeal membrane oxygenation". Crit Care Med. 26 (2): 409–14. PMID 9468181.
- ↑ 17.0 17.1 17.2 Ulloa-Morrison R, Vial PA, Vial C, Ferrés M, Mertz GJ (2024). "Critical care management of hantavirus cardiopulmonary syndrome". J Crit Care. 84: 154878. doi:10.1016/j.jcrc.2024.154878. PMID 39024823 Check
|pmid=value (help). - ↑ 18.0 18.1 Kraft L, Stand T, Stand A, Banas B, Zimmermann M (2026). "Long-term follow-up after nephropathia epidemica: a retrospective cohort study". Nephrol Dial Transplant. doi:10.1093/ndt/gfaf073. PMID 41070942 Check
|pmid=value (help). - ↑ 19.0 19.1 19.2 19.3 Mills JN, Corneli A, Young JC, Garrison LE, Khan AS, Ksiazek TG (2002). "Hantavirus pulmonary syndrome--United States: updated recommendations for risk reduction. Centers for Disease Control and Prevention". MMWR Recomm Rep. 51 (RR-9): 1–12. PMID 12194506.
- ↑ Janwadkar RS, Patel KR, Patel JA (2025). "Hantavirus in pregnancy: a case report and review". J Emerg Med. PMID 40857994 Check
|pmid=value (help). - ↑ "Hantavirus pulmonary syndrome in five pediatric patients--four states, 2009". MMWR Morb Mortal Wkly Rep. 58 (50): 1409–12. 2009. PMID 20032925.
- ↑ Levy H, Simpson SQ (1994). "Hantavirus pulmonary syndrome". Am J Respir Crit Care Med. 149 (6): 1710–3. doi:10.1164/ajrccm.149.6.8004332. PMID 8004332.