Hantavirüs Pulmoner Sendromu ile Hemorajik Ateş: Temel Farklar (HPS vs HFRS)

Hantavirus infection produces two distinct clinical syndromes that differ in the organ they target, the region of the world in which they occur, their case-fatality rates, and the strain of virus responsible. Hantavirus pulmonary syndrome (HPS) is the New World disease — dominated by the lungs and caused by Andes virus (ANDV) and Sin Nombre virus (SNV). Hemorrhagic fever with renal syndrome (HFRS) is the Old World disease — dominated by the kidneys and caused primarily by Hantaan, Seoul, Puumala, and Dobrava viruses. The MV Hondius outbreak is HPS caused by Andes virus. Understanding which syndrome is in play changes the clinical approach immediately.

1. The geography explains the split

The division between HPS and HFRS maps almost exactly onto the division between the Americas and the rest of the world. Rodent reservoirs carrying New World hantaviruses evolved on the American continent alongside their hosts; Old World strains evolved in Eurasia and Africa. Seoul virus is the partial exception — carried by the cosmopolitan brown and black rats, it can be found on every inhabited continent, though it tends to cause milder HFRS than Hantaan or Dobrava.

New World HPS-causing strains include Sin Nombre virus (reservoir: deer mouse, Peromyscus maniculatus), responsible for most HPS cases in the United States, and Andes virus (reservoir: long-tailed rice rat, Oligoryzomys longicaudatus), responsible for HPS in Chile and Argentina — including the MV Hondius cluster. Over a dozen other Americas-based strains have been identified that cause HPS, but SNV and ANDV account for the overwhelming majority of severe cases.

Old World HFRS strains include Hantaan virus (reservoir: striped field mouse, Apodemus agrarius, found across eastern Asia), Puumala virus (reservoir: bank vole, Myodes glareolus, found across Europe), and Dobrava virus (reservoir: yellow-necked mouse,Apodemus flavicollis, associated with severe European HFRS). Together, HFRS causes an estimated 150,000–200,000 hospitalisations globally each year, the majority in China.

2. Organ targets: lungs vs kidneys

The fundamental difference between HPS and HFRS comes down to where in the body the hantavirus-driven capillary leak is most severe. Hantaviruses infect the endothelial cells lining small blood vessels. When the immune response triggers capillary permeability, fluid leaks into whatever tissue surrounds the most affected vasculature.

In HPS, the leak is predominantly pulmonary. Fluid accumulates in the alveolar spaces, causing a form of non-cardiogenic pulmonary oedema that can fill the lungs within hours. Gas exchange collapses; hypoxic respiratory failure follows. The kidneys are often mildly affected in HPS but are not the primary site of damage.

In HFRS, the leak is predominantly renal. Vascular injury in the kidney causes acute kidney injury — manifesting first as a drop in urine output, then as a cascade of electrolyte abnormalities, haemorrhagic diathesis, and, in severe cases, shock. The lungs can be mildly involved in HFRS, but respiratory failure is not the hallmark.

3. Symptom progression: two-phase vs five-phase

HPS follows a two-phase course. The first phase is a febrile prodrome lasting three to seven days: fever, myalgia, headache, and often gastrointestinal symptoms. The second phase is the cardiopulmonary phase: rapid-onset dyspnoea, hypoxaemia, haemodynamic instability. The transition between phases can be abrupt — within hours.

HFRS follows a five-phase course that tends to unfold over a longer and more predictable timeline:

1. Febrile phase (days 1–7) — fever, malaise, headache, blurred vision, facial flushing, petechiae
2. Hypotensive phase (hours to days) — drop in blood pressure, tachycardia, abdominal or back pain; haemorrhage in severe cases
3. Oliguric phase (3–7 days) — reduced urine output, rising creatinine and urea; risk of fluid overload and pulmonary oedema
4. Polyuric phase (days to weeks) — abrupt increase in urine output as kidney function begins to recover; risk of dehydration and electrolyte imbalance
5. Convalescent phase (weeks to months) — gradual return to normal kidney function; fatigue may persist

Not all patients pass through every phase. Mild Puumala HFRS (called nephropathia epidemica in Scandinavia) may never produce severe hypotension and often resolves without hospitalisation. Hantaan and Dobrava HFRS are substantially more severe and can follow the five-phase course with clinical crises at each transition.

4. Bleeding: a marker for HFRS, not HPS

Haemorrhagic manifestations are a defining feature of HFRS, not HPS. Patients with severe Hantaan or Dobrava HFRS can develop petechiae (tiny skin haemorrhages), mucosal bleeding, and, in the worst cases, spontaneous haemorrhage from the adrenal glands. Thrombocytopenia is common and can be severe.

HPS patients also develop thrombocytopenia — indeed, a falling platelet count is one of the earliest laboratory signals of impending cardiopulmonary deterioration in HPS — but frank haemorrhage is uncommon. The clinical picture in HPS is dominated by respiratory and haemodynamic collapse, not bleeding.

A patient presenting after possible Andes virus exposure with prominent petechiae, mucosal bleeding, and acute kidney injury but minimal respiratory symptoms should prompt consideration of Seoul virus or another HFRS-associated strain, or an alternative diagnosis entirely.

5. Case-fatality rates: HPS is deadlier

The raw case-fatality rate (CFR) for HPS caused by Sin Nombre virus is approximately 35–40% in the United States, based on CDC surveillance data. Andes virus HPS in South America carries a somewhat lower published CFR — closer to 25–35% — though figures vary by study period and healthcare access. The MV Hondius cluster had a CFR of approximately 21% as of mid-May 2026, which may reflect early detection and transfer to capable ICUs for a proportion of cases.

HFRS CFR spans a much wider range depending on the causative strain:

• Puumala HFRS (Europe): CFR below 0.5% in most series; most patients recover fully
• Seoul HFRS (global): CFR approximately 1–2%
• Hantaan HFRS (East Asia): CFR 1–5% in hospitalised patients in endemic areas with experienced centres; higher in outbreak contexts or with delayed care
• Dobrava HFRS (Balkans): CFR up to 12–15% in severe Dobrava genotype A cases; lower for genotype Kurkino

The practical implication is that HPS is a medical emergency with a meaningful chance of death even with good ICU care. HFRS carries a range of outcomes from mild outpatient illness (Puumala) to a serious hospitalisation with real mortality risk (Hantaan, Dobrava). Both syndromes benefit from early recognition and appropriate escalation, but the urgency and the organ to monitor differ.

6. Person-to-person transmission: only ANDV

One critical difference between specific strains that cuts across the HPS/HFRS divide: only Andes virus has demonstrated reliable evidence of person-to-person transmission. All other hantaviruses — including all HFRS-causing strains and other HPS-causing strains such as Sin Nombre — are transmitted exclusively from rodent to human, and do not spread between people.

This has direct implications for isolation and contact-tracing protocols. A patient with Hantaan HFRS does not require droplet or contact isolation beyond standard precautions. A patient with confirmed or suspected ANDV HPS requires airborne precautions and full contact tracing of close contacts, as the MV Hondius response has demonstrated.

7. Diagnosis: which tests, in which order

Both HPS and HFRS are confirmed by serology (IgM and IgG ELISA) or RT-PCR on whole blood or serum. IgM antibodies are typically detectable at or shortly after symptom onset in both syndromes. RT-PCR has highest sensitivity in the first five days of illness when viraemia is highest; sensitivity declines as the immune response clears the virus from blood.

The initial laboratory findings differ in a way that reflects the organ involvement:

• HPS: thrombocytopenia, haemoconcentration (high haematocrit), left-shifted neutrophilia with immunoblasts on peripheral smear, low albumin. Chest x-ray or CT shows bilateral pulmonary infiltrates (interstitial oedema).
• HFRS: thrombocytopenia, rising serum creatinine and urea, proteinuria, microscopic haematuria. Imaging may show retroperitoneal oedema and renal enlargement. In severe cases, elevated liver enzymes and coagulation abnormalities.

In practice, a clinician in Western Europe seeing a patient with fever, thrombocytopenia, and acute kidney injury who recently camped in rural Finland should order Puumala serology. The same clinician seeing a passenger from the MV Hondius with fever, falling platelet count, and new dyspnoea should order ANDV serology (and RT-PCR if within five days of symptom onset) and prepare for ICU escalation.

8. Treatment differences

Neither HPS nor HFRS has an approved antiviral treatment as of 2026. Ribavirin has shown benefit for Old World HFRS caused by Hantaan virus in a randomised controlled trial, and some centres use it empirically for severe HFRS in the febrile phase. For HPS, randomised evidence for ribavirin is absent and retrospective series have not shown benefit.

The supportive-care approach also differs by syndrome:

• HPS: ICU-level monitoring, conservative fluid strategy (aggressive fluid resuscitation worsens pulmonary oedema), lung-protective mechanical ventilation, vasopressors, ECMO as rescue therapy in severe cases.
• HFRS: careful fluid balance through the oliguric phase (risk of both dehydration during hypotension and fluid overload during oliguria), renal replacement therapy (dialysis) if creatinine rises sharply, and aggressive rehydration during the polyuric phase. Dialysis is required in 5–20% of hospitalised Hantaan HFRS cases.

9. At-a-glance comparison

10. Frequently asked questions

Can one patient have both HPS and HFRS simultaneously?

Co-infection with two different hantavirus strains is theoretically possible but extremely rare. More commonly, a patient infected with Hantaan virus may show both pulmonary and renal involvement because even Old World strains cause some degree of systemic endothelial damage. However, the dominant syndrome generally matches the infecting strain.

Is Seoul virus infection dangerous?

Seoul virus causes relatively mild HFRS compared with Hantaan and Dobrava. Most hospitalised cases recover fully. Case fatality is estimated at 1–2%. It is the only hantavirus with a truly global distribution, having spread with the commensal rat populations.

Why is HPS so much deadlier than most HFRS?

The speed of respiratory failure in HPS and the limitations of mechanical ventilation against a non-cardiogenic pulmonary oedema driven by viral immunopathology explain much of the gap. The kidneys in HFRS can be supported with dialysis; the lungs in severe HPS can only be bypassed with ECMO, which is resource-intensive and not universally available. The CFR for Puumala HFRS approaches zero partly because the disease is intrinsically milder, not just because it receives better care.