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.
ReviewHantavirus Infections in Europe
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
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