Review
Hantavirus Infections in Europe

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Summary

Hantaviruses are enveloped RNA viruses each carried by a specific rodent species. Three hantaviruses, Puumala, Dobrava, and Saaremaa viruses, are known to cause haemorrhagic fever with renal syndrome. In Europe, Puumala causes a generally mild disease, nephropathia epidemica, which presents most commonly with fever, headache, gastrointestinal symptoms, impaired renal function, and blurred vision, whereas Dobrava infections often also have haemorrhagic complications. There are few available data about the clinical picture of confirmed Saaremaa infections, but epidemiological evidence suggests that it is less pathogenic than Dobrava, and that Saaremaa infections are more similar to nephropathia epidemica caused by Puumala. Along with its rodent host, the bank vole (Clethrionomys glareolus), Puumala is reported throughout most of Europe (excluding the Mediterranean region), whereas Dobrava, carried by the yellow-necked mouse (Apodemus flavicollis), and Saaremaa, carried by the striped field mouse (Apodemus agrarius), are reported mainly in eastern and central Europe. The diagnosis of acute hantavirus infection is based on the detection of virusspecific IgM. Whereas Puumala is distinct, Dobrava and Saaremaa are genetically and antigenically very closely related and were previously thought to be variants of the same virus. Typing of a specific hantavirus infection requires neutralisation antibody assays or reverse transcriptase PCR and sequencing.

Section snippets

General properties of hantaviruses

Hantaviruses are rodent-borne enveloped RNA viruses with a diameter of 120 nm belonging to the family Bunyaviridae.23 Each hantavirus is carried by a specific rodent species and transmission to other species (including people) is a deadend for the virus. The three-segmented, negative-strand, approximately 12 kb long RNA genome of hantaviruses codes for four proteins. The small (S), medium (M), and large (L) RNA segments encode a nucleocapsid protein, two glycoproteins (G1, G2), and an RNA

Hantaviruses and their carrier rodents

Puumala along with its host, the bank vole, is found all over Europe, excluding the Mediterranean coastal regions and most of the Iberian Peninsula and Greece (figure 2A). The dynamics of bank voles differ geographically. In northern Europe (Fennoscandia), the bank vole generally has population density cycles of 3–4 years, probably due mainly to predators. During the late increase and peak phases of the population cycle, bank vole densities are high from late summer of the increase year to late

Human epidemiology

Puumala is the most common cause of HFRS in Europe with an average of 1000 serology-verified cases annually in Finland (incidence 19 per 100 000), 100–300 in Sweden, and around 50 in Norway (in 1998, over 200 cases) (table 2). The average Puumala seroprevalence in Finland is 5% (in eastern Finland, 11%),40 and 5–9% in northern Sweden.41 In southern Sweden, where bank vole populations are non-cyclic, the disease is very rare. In Estonia, antibodies to Puumala are present in 5·1%, and to Saaremaa

Clinical picture of hantavirus diseases in Europe

At present, three pathogenic hantaviruses are known to circulate in Europe, all causing HFRS: Puumala, Dobrava, and Saaremaa. The incubation period is 2–4 weeks. Typically, the course of HFRS has been divided into febrile, hypotensive, oliguric, diuretic, and convalescent phases, but these phases are not always clinically evident. The course of the infection varies from subclinical to fatal, and the infection is generalised and can affect several organs.

Puumala infection, or nephropathia

Immunity and control

Infection is thought to leave a lifelong immunity and hantavirus antibodies can be seen decades after infection.25, 99 Cytotoxic T-cells, mainly specific to the central region of the N protein, are often seen years after Puumala infection.100 Whether a previous Puumala infection protects from Dobrava or Saaremaa infection or vice versa is not known. Vaccines based on inactivated viruses (HTNV, SEOV) have been developed and widely used in China and Korea. The Korean “Hantavax” was also used in

Pathogenesis

The key element to most symptoms of both HFRS and HPS is increased capillary permeability. Hantavirus replication occurs in the vascular endothelium102, 103 but does not seem to cause direct cytopathic effects. CD8+ T lymphocytes together with monocyte/macrophages have been seen in the kidneys of nephropathia epidemica patients104 and in association with hantavirus-positive lung endothelial cells of HPS patients.103 CD8+ and CD4+ cytotoxic T-lymphocytes targeted to the abundantly expressed

Laboratory diagnostics

The diagnostics of Puumala, Dobrava, and Saaremaa infections are based on serology. Even during the first days of the disease, IgM and usually also IgG antibodies are present. However, in rare cases (<2%) Puumala IgM antibodies have been negative up to 5 days after onset of illness.119 The early IgG response is predominantly directed towards the nucleocapsid protein.25, 120, 121 Immunofluorescence assays based on native viral antigen grown in cell culture have been widely used for diagnostics,

Concluding remarks

Hantavirus diseases are present in most of Europe and diagnosing them depends on clinical alert and use of serological tests. By mapping endemic areas with more detailed surveillance of European rodents, development of more rapid and sensitive tests, and increased clinician awareness, human hantavirus infections will presumably be detected in new areas and new rodent species might be seen to carry yet unknown hantaviruses. However, reports based on isolation or RT-PCR without reliable sequence

Search strategy and selection criteria

Data for this review were selected by searches of Medline and references from relevant articles and from the files of the authors. Search terms were “hantavirus” and “haemorrhagic fever with renal syndrome” with restriction to mainly English papers concerning epidemiology and infections in Europe.

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