Hantavirus infections.

Over the past few decades understanding and recognition of hantavirus infection has greatly improved worldwide, but both the amplitude and the magnitude of hantavirus outbreaks have been increasing. Several novel hantaviruses with unknown pathogenic potential have been identified in a variety of insectivore hosts. With the new hosts, new geographical distributions of hantaviruses have also been discovered and several new species were found in Africa. Hantavirus infection in humans can result in two clinical syndromes: haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) caused by Old World and New World hantaviruses, respectively. The clinical presentation of HFRS varies from subclinical, mild, and moderate to severe, depending in part on the causative agent of the disease. In general, HFRS caused by Hantaan virus, Amur virus and Dobrava virus are more severe with mortality rates from 5 to 15%, whereas Seoul virus causes moderate and Puumala virus and Saaremaa virus cause mild forms of disease with mortality rates <1%. The central phenomena behind the pathogenesis of both HFRS and HCPS are increased vascular permeability and acute thrombocytopenia. The pathogenesis is likely to be a complex multifactorial process that includes contributions from immune responses, platelet dysfunction and the deregulation of endothelial cell barrier functions. Also a genetic predisposition, related to HLA type, seems to be important for the severity of the disease. As there is no effective treatment or vaccine approved for use in the USA and Europe, public awareness and precautionary measures are the only ways to minimize the risk of hantavirus disease.

Viral load and immune response dynamics in patients with haemorrhagic fever with renal syndrome.

Haemorrhagic fever with renal syndrome (HFRS) in Slovenia can be caused by infection with either Dobrava (DOBV) or Puumala (PUUV) virus, but a clear difference in disease severity is observed. We hypothesized that the wide spectrum of disease observed among HFRS patients might be related to differing immune responses and viral load kinetics. To test this hypothesis we analysed sequential blood samples from 29 HFRS patients hospitalized in Slovenia. Measuring viral RNA in patient samples revealed that viraemia lasts for longer than previously believed, with DOBV or PUUV-infected patients having viraemias lasting on average 30 days or 16 days, respectively. DOBV-infected patients were found to have a higher viral load than the PUUV-infected patients (10(7) vs. 10(5) RNA copies/mL). Both DOBV and PUUV-infected patients had IgM at the time of hospital admission, but there was a difference in IgG antibody dynamics, with only a minority of DOBV-infected patients having IgG antibodies. In our study, elevated levels of IL-10, TNF-α and IFN-γ were detected in all of the samples regardless of the causative agent. In DOBV-infected patients the decrease in cytokine secretion level appeared around day 20 post-infection, while in PUUV-infected patients the change was earlier. In general, our findings point toward notable differences between PUUV and DOBV infections, in terms of viral load and antibody and cytokine response dynamics, all of which may be reflected in differing disease severities and clinical outcomes.