What are hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS)?

Hantavirus Pulmonary Syndrome and Hemorrhagic Fever with Renal Syndrome

Hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS) are two distinct clinical manifestations of hantavirus infection—HPS occurs exclusively in the Americas causing severe respiratory failure with high mortality, while HFRS occurs in Europe and Asia causing primarily kidney failure with hemorrhagic complications. 1, 2

Geographic Distribution and Causative Viruses

Hantavirus Pulmonary Syndrome (HPS)

• Restricted to the Americas due to its sigmodontine rodent hosts 2
• Primary causative agent in the United States: Sin Nombre virus (SNV), hosted by the deer mouse (Peromyscus maniculatus) 2
• Other HPS-causing viruses include New York virus, Black Creek Canal virus, and Bayou virus 2
• Approximately 20-50 cases confirmed annually in the United States since 1993 2

Hemorrhagic Fever with Renal Syndrome (HFRS)

• Occurs in Europe and Asia, caused by murine and arvicoline rodent-associated hantaviruses 2
• Severe forms caused by Hantaan and Dobrava viruses with case fatality rates up to 10% 2
• Mild forms include Seoul virus (mortality <1%) and Puumala virus causing nephropathia epidemica (NE) in northern Europe (mortality <1%) 2

Clinical Presentation

HPS Clinical Features 1

HPS is a febrile illness characterized by:

• Temperature >101.0°F (>38.3°C)
• Bilateral diffuse interstitial pulmonary edema resembling ARDS
• Respiratory compromise requiring supplemental oxygen, developing within 72 hours of hospitalization
• Occurs in previously healthy individuals

Prodromal symptoms include:

• Fever, chills, myalgia, headache
• Gastrointestinal symptoms

Laboratory findings:

• Hemoconcentration
• Left shift in white blood cell count with neutrophilic leukocytosis
• Thrombocytopenia
• Circulating immunoblasts

HFRS Clinical Features 3, 4

HFRS presents with:

• High fever and body pain
• Pronounced renal dysfunction leading to acute kidney injury
• Less prominent respiratory involvement compared to HPS
• Thrombocytopenia
• Hemorrhagic findings

Pathophysiology

Both syndromes share a common underlying mechanism: 3, 5

• Vascular dysregulation leading to increased capillary permeability
• Vessel leakage and potential shock
• Endothelial cells are the primary target of infection
• No direct cell damage from viral replication has been documented

The pathogenesis involves immune-mediated mechanisms rather than direct viral cytopathic effects 3. Recent evidence suggests considerable clinical overlap exists between HPS and HFRS, with both representing a spectrum of the same disease process 5.

Transmission 2

Primary route: Inhalation of infectious aerosolized rodent saliva, urine, or feces

Additional routes:

• Direct introduction through broken skin or conjunctivae
• Possible ingestion in contaminated food or water
• Rodent bites (documented for both HPS and HFRS)

Important caveat: Person-to-person transmission is generally NOT documented for HPS in the United States or for any HFRS-causing viruses, with the notable exception of Andes virus in Argentina, where nosocomial transmission has been well-documented 2

Diagnosis 1

Laboratory confirmation requires one of the following:

• Detection of hantavirus-specific IgM or rising IgG titers
• Detection of hantavirus-specific RNA by PCR in clinical specimens
• Detection of hantavirus antigen by immunohistochemistry

Critical point: Laboratory testing should be performed or confirmed at a reference laboratory due to the nonspecific nature of clinical illness and the commonness of ARDS from other causes 1

Key Clinical Distinctions

HPS is characterized by:

• More pro-inflammatory cytokine profile 6
• Upregulation of 40 cytokines (vs 21 in HFRS)
• Strong activation of innate immune and Th1-type responses
• Primary target organ: lungs

HFRS is characterized by:

• Dichotomy in serum cytokine levels 6
• Primary target organ: kidneys
• Variable severity depending on viral strain

Both conditions can have long-term sequelae and require supportive care focused on maintaining cardiovascular, respiratory, and renal function 4.