title: [Grading the severity of disease in patients with Puumala or Dobrava virus infections from 1995 to 2000 in Croatia].
abstract: OBJECTIVE
  The aim of our study was to evaluate the proposed Croatian scale for grading the disease severity in patients with hemorrhagic fever with renal syndrome (HFRS). The aim was also to determine whether the infection with Dobrava virus (DOBV) in Croatia was associated with a more severe illness than the infection with Puumala virus (PUUV).
  
  
  METHODS
  To evaluate the scale, case records of 62 HFRS patients hospitalized at the University Hospital for Infectious Diseases in Zagreb from 1995 till 2000 were reviewed. ELISA IgM and IgG tests were used for the detection of specific IgM and IgG antibodies to PUUV or DOBV.
  
  
  CONCLUSIONS
  HFRS caused by hantaviruses is a zoonotic disease spread worldwide, posing a major public health problem of global dimensions. Recent epidemiologic studies show that almost all parts of Croatia are endemic regions for two hantaviruses, Puumala and Dobrava. The disease severity ranges from subclinical infection to severe illness with fatal outcome. Clinical picture is predominated by fever, myalgia, vomiting, hemorrhagic manifestation, visual impairment and kidney affection. There is still a lack of knowledge concerning all the parameters involved in the disease severity. Besides the type of virus and genetic material, host genes are also associated with the variable clinical course. HLA alleles B8, DR3, and DQ2 are strongly associated with severe outcome of PUUV infection, white HLA B27 allele is associated with a mild course. Whether similar genetic factors also operate in DOBV infection remains to be determined. Recently, a Croatian scale for grading the disease severity was proposed. The disease severity is graded by a scoring system (points attributed to specific clinical symptoms and laboratory findings) as 1--mild, 2--moderate, 3--severe, and 4--very severe. We found 60% of HFRS patients to be infected with PUUV and 40% with DOBV. In our study, 65% of patients infected with PUUV had mild, and 24% moderate disease. Severe and very severe disease was recorded in 11% of PUUV infected patients. In contrast, only 44% of patients infected with DOBV had mild disease, whereas 40% of patients showed a moderate clinical picture. Severe and very severe clinical picture was recorded in 16% of patients with DOBV infection. Statistical analysis showed a significant number of pa (p < 0.01) with PUUV infection to have mild disease, whereas a significant number of HFRS patients infected with DOBV had moderate (p < 0.01) and severe or very severe (p < 0.01) disease.
  
  
  CONCLUSIONS
  Our results clearly indicate that in Croatia DOBV infection is associated with a more severe disease than PUUV infection. However, we confirmed previous findings that even PUUV infection could lead to a severe disease. Our initial experience in the evaluation of the proposed grading scale for disease severity demonstrated the proposed Croatian scale to be a useful tool in grading disease severity in patients infected with PUUV or DOBV. Moreover, the proposed scale may also prove highly useful for the prognostic purpose.
authors.affiliation: Odsjek za celularnu imunologiju Odjel za istrazivanje i razvoj Imunoloski zavod Rockefellerova 10 10000 Zagreb, Hrvatska. lcebalo@imz.hr
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Cebalo
authors.forename: Tina
authors.initials: T
authors.lastname: Dusek
authors.forename: Ilija
authors.initials: I
authors.lastname: Kuzman
authors.forename: Alemka
authors.initials: A
authors.lastname: Markotić
mesh_terms: D000914:Antibodies, Viral / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D006476:Orthohantavirus / Q000276:immunology; D018778:Hantavirus Infections / Q000145:classification* / Q000175:diagnosis; D006480:Hemorrhagic Fever with Renal Syndrome / Q000145:classification* / Q000175:diagnosis; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D029262:Puumala virus / Q000276:immunology; D012720:Severity of Illness Index
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M