HPS vs HFRS: Two Faces of Hantavirus Disease Compared
Hantavirus Pulmonary Syndrome (HPS) and Hemorrhagic Fever with Renal Syndrome (HFRS) compared: causative viruses, geography, symptoms, fatality, treatment.
Hantaviruses cause two distinct human syndromes that share a virus family but differ in geography, clinical course, and case-fatality: Hantavirus Pulmonary Syndrome (HPS) in the Americas and Hemorrhagic Fever with Renal Syndrome (HFRS) in Eurasia. Understanding the contrast is essential for travel medicine, differential diagnosis, and emergency-response planning.
Side-by-side comparison
| Feature | HPS | HFRS |
|---|---|---|
| Geography | Americas | Eurasia |
| Major species | Sin Nombre, Andes, Black Creek Canal, Bayou | Hantaan, Seoul, Puumala, Dobrava |
| Reservoirs | Sigmodontinae rodents (deer mouse, rice rat) | Murinae and Arvicolinae (field mouse, bank vole, Norway rat) |
| Incubation | 1–8 weeks (median 2–4) | 1–6 weeks (median 2–3) |
| Primary organ | Lung (capillary leak) | Kidney (acute injury) |
| Hallmark sign | Non-cardiogenic pulmonary edema | Polyuric phase + bleeding |
| Case-fatality | 30–40% | <1% (Puumala) to ~12% (Hantaan) |
| Person-to-person | Only Andes virus | None confirmed |
| Vaccine | None | Hantavax (S. Korea, China) |
| Antiviral | Supportive only | Ribavirin (within 4 days) |
Clinical phases of HFRS
HFRS unfolds in five classical phases (most clearly seen with Hantaan virus; Puumala produces a milder variant called nephropathia epidemica):
- Febrile (3–7 days) — abrupt fever, headache, abdominal pain, facial flushing, conjunctival injection.
- Hypotensive (hours–2 days) — capillary leak, shock, thrombocytopenia.
- Oliguric (3–7 days) — acute kidney injury, hemorrhage in mucous membranes and viscera.
- Polyuric (days–weeks) — diuresis, electrolyte derangement.
- Convalescent — gradual recovery, occasional residual hypertension.
Clinical phases of HPS
- Prodromal (3–7 days) — fever, severe myalgia (thighs, hips, lumbar), headache, GI symptoms.
- Cardiopulmonary (hours) — abrupt dyspnea, hypotension, profuse pulmonary edema; lactate climbs sharply.
- Diuretic / convalescent — survivors often turn the corner within 24–48 hours of stabilization with rapid resolution of edema.
Differential diagnosis pearls
- HPS vs ARDS / atypical pneumonia — thrombocytopenia + hemoconcentration (rising hematocrit) + immunoblasts on CBC point to HPS.
- HFRS vs leptospirosis — both cause AKI plus thrombocytopenia. Geographic exposure history is decisive: rural rodent exposure for HFRS, freshwater wading for leptospirosis.
- Puumala vs other HFRS — Puumala (nephropathia epidemica) is much milder, often without bleeding; common in Finland, Sweden, western Russia.
Vaccines: state of the art
Hantavax, a bivalent inactivated vaccine derived from suckling-mouse brain, has been licensed in South Korea since 1990 and in China since 2009 for HFRS prevention. Field-effectiveness data remain mixed; modern candidates using DNA platforms and adenovirus-vectored constructs are in trial. No HPS vaccine has entered Phase III; an ANDV DNA vaccine completed Phase IIa with an acceptable safety profile.
For deeper context
Frequently asked
What is the difference between HPS and HFRS?
HPS (Hantavirus Pulmonary Syndrome) occurs in the Americas, attacks the lungs with case-fatality 30–40%. HFRS (Hemorrhagic Fever with Renal Syndrome) occurs in Eurasia, attacks the kidneys with CFR <1% (Puumala) to ~12% (Hantaan).
Are HPS and HFRS caused by the same virus?
No. They are caused by different species in the same Hantavirus genus. HPS is caused mainly by Sin Nombre and Andes viruses; HFRS by Hantaan, Seoul, Puumala, and Dobrava viruses.
Is there a vaccine for HFRS?
Hantavax, a bivalent inactivated vaccine, is licensed in South Korea (1990) and China (2009) for HFRS. It does not protect against New World hantaviruses or HPS.
Does ribavirin work against hantavirus?
Ribavirin shows efficacy against HFRS when started within 4 days of symptom onset. Evidence for HPS is more equivocal, and ribavirin is not standard of care for HPS.
Why does HPS have such a high case-fatality?
HPS produces rapid non-cardiogenic pulmonary edema and cardiogenic shock within hours of cardiopulmonary phase onset, leaving little time for transfer to ECMO-capable centers. Case-fatality drops materially when patients reach experienced tertiary care early.
Related explainers
- → Hantavirus — Complete GuideComprehensive guide to hantavirus: symptoms, transmission via rodents, HPS vs HFRS, mortality rates, treatment, and the 2026 outbreak signal.
This article is editorial research aggregated from public health authorities. It is not medical advice. For clinical concerns, consult a healthcare professional. Sources: WHO, CDC, ECDC, PAHO.