Hantavirus infection (nephropathia epidemica)

Definition

Hantavirus diseases are zoonoses caused by viruses of the genus Orthohantavirus, transmitted from rodents to humans. European and Asian virus types cause hemorrhagic fever with renal syndrome (HFRS). The types found in Germany, Puumala virus and Dobrava-Belgrade virus (Kurkino genotype), usually cause a milder form, nephropathia epidemica.

Occurrence & epidemiology

In Germany, Puumala virus infections predominate mainly in the south and west, Dobrava-Kurkino infections in the east and north. More than two thirds of patients are men, more than half of them aged 30 to 49 years; children are very rarely affected. Seroprevalence in the population is about 1%. Reported case numbers vary widely (between 72 cases in 2006 and 2,825 cases in 2012); about every 2–3 years there are outbreak years with regional clusters, e.g. in the Swabian Jura, the Bavarian Forest, the Spessart and the Münsterland.

Aetiopathogenesis

The reservoir of Puumala virus is the bank vole, that of Dobrava-Kurkino virus the striped field mouse. Infected rodents shed the virus in saliva, urine and feces, where it remains infectious for several days even when dried. Humans are infected mainly by inhaling virus-containing dust (e.g. when cleaning basements, attics or sheds), less often through injured skin, bites or contaminated food. The incubation period is usually 2–4 weeks (5 to 60 days).

Clinical features

Many infections are asymptomatic or nonspecific. Nephropathia epidemica begins suddenly like a biphasic flu-like illness with high fever, headache, back and abdominal pain, colicky, often unilateral flank pain, nausea and diarrhea. Visual disturbances (transient myopia, photophobia) and conjunctival hemorrhages are typical; generalized bleeding is extremely rare.

Proteinuria (0.1 to more than 20 g/L) and microscopic hematuria are almost always present. Acute kidney dysfunction occurs on average after 7 days (3–19 days), with oliguria followed by a polyuric phase. Permanent chronic kidney failure is rare. In the more severe HFRS caused by other virus types, hypotension, shock, bleeding and pulmonary involvement occur.

Histology

Kidney biopsies show interstitial nephritis with a mononuclear infiltrate and occasionally interstitial, mainly medullary hemorrhage. In uncomplicated cases, a biopsy is usually not required.

Diagnosis

The combination of several of the following findings suggests hantavirus disease:

• acute onset with fever > 38.5 °C
• back, head and/or abdominal pain
• proteinuria and/or hematuria
• thrombocytopenia
• rise in serum creatinine during the course
• oliguria followed by polyuria

Laboratory tests: moderate rise in creatinine, CRP and white cells, thrombocytopenia < 100 × 10⁹/L and tubular proteinuria with increased alpha-1-microglobulin. The diagnosis is confirmed serologically by IgM and IgG antibodies (ELISA, immunoblot or immunofluorescence), testing with Puumala and Dobrava antigens in Europe. IgM is usually detectable at symptom onset, IgG in 80–90% of samples taken in the first 5 days. Blood PCR is informative only in the early, short viremic phase; a negative result does not exclude infection.

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Further reading (open access)

1. RKI-Ratgeber: Hantavirus-Erkrankung
2. MSD Manual Professional: Hantavirus Infection

Cross-references