title: [The biggest epidemic of hemorrhagic fever with renal syndrome in Croatia].
abstract: BACKGROUND
  The largest outbreak of hemorrhagic fever with renal syndrome (HFRS) to date occurred in Croatia in the year 2002. The epidemic started in winter, lasted throughout spring to summer months, ending not earlier than November.
  
  
  OBJECTIVE
  The aim of this study was to investigate and analyze the basic epidemiologic and clinical features of HFRS in Croatia by uniform and standardized prospective-retrospective analysis of all patients affected by the epidemic.
  
  
  METHODS
  When the epidemic started, a patient questionnaire with questions on the basic demographic data, site of infection and other epidemiologic characteristics, clinical symptoms, disease severity and laboratory results was designed. Data on 401 patient with a clinical diagnosis of HFRS were collected. The etiologic diagnosis of the disease was confirmed by ELISA, and in some patients by indirect immunofluorescence test (IFT). The results were analyzed using a descriptive statistical method.
  
  
  RESULTS
  HFRS was clinically diagnosed in 401 patients from all over Croatia. A total of 320 (79.8%) cases were reported to the Epidemiology Service of the National Institute of Public Health. The majority of patients (n = 128) were registered in June. Males were three times more affected than females. Apart from its long duration, this epidemic was characteristic for the involvement of general population, with only a small number of the affected from the potential risk groups (forestry workers 28, soldiers 14, farmers 18). The epidemic spread almost throughout inland Coratia. At least 44 patients were infected in the Plitvice Lakes area, 32 in Slunj, 27 on Sljeme, 24 in Velika, and at least 19 in the area of Kutjevo. The youngest patient was aged 4 and the oldest 80 years. The majority of patients were treated in Zagreb (University Hospital for Infectious Diseases--110, Zagreb University Hospital Center--3), followed by Karlovac (71 inpatients and 39 outpatients), Pozega (n = 79), and Rijeka (n = 37). Serologic analysis (ELISA method) detected Puumala virus in 161 and Dobrava virus in only 17 patients. The disease was confirmed by immunofluorescence method in 53 patients (mostly in Kariovac). During the 2002 outbreak, HFRS clinically manifested mostly in a milder form with general symptoms and transitory renal insufficiency, while hemorrhages were rarely recorded. According to our disease severity score, a mild form of the disease was recorded in 65%, moderately severe in 28%, severe in 5% and extremely severe form in 2% of the patients. One patient died. Two thirds of the patients were hospitalized during the febrile stage of the disease. All patients had fever, whereas headache and pain in the lumbar region were recorded in more than 90% of cases, polyuria in 75%, oliguira and vomiting in approximately 50%, respiratory symptoms in 35%, and hemorrhages (mostly on the skin and mucous membranes), vision disturbances, conjunctivitis and diarrhea in approximately 25% of patients. ESR was elevated in 64% and CRP in 93% of patients. Leukocytosis was recorded in 25% and thrombocytopenia in 70% of patients. Increased values of urea and creatinine and signs of liver damage were recorded in approximately 50% of the patients.
  
  
  CONCLUSIONS
  The largest outbreak of HFRS occurred in Croatia in 2002, with more than 400 diseased throughout Croatia. This epidemic confirmed our previous assumption that the whole Croatia, apart from its narrow coastline area and islands, is a natural focus of HFRS with different causative types of hantaviruses. Efforts should be made to conduct a comprehensive ecologic and mammologic study on hantaviruses and their biologic characteristics in these areas.
authors.affiliation: Klinika za infektivne bolesti Dr. Fran Mihaljevic Mirogojska 8 10000 Zagreb, Hrvatska. ikuzman@net.hr
authors.forename: Ilija
authors.initials: I
authors.lastname: Kuzman
authors.forename: Ivan
authors.initials: I
authors.lastname: Puljiz
authors.forename: Drago
authors.initials: D
authors.lastname: Turcinov
authors.forename: Alemka
authors.initials: A
authors.lastname: Markotić
authors.forename: Branko
authors.initials: B
authors.lastname: Turković
authors.forename: Borislav
authors.initials: B
authors.lastname: Aleraj
authors.forename: Zdravko
authors.initials: Z
authors.lastname: Andrić
authors.forename: Dobrinka
authors.initials: D
authors.lastname: Petković
authors.forename: Vesna
authors.initials: V
authors.lastname: Tutek
authors.forename: Boris
authors.initials: B
authors.lastname: Herendić
authors.forename: Miljenko
authors.initials: M
authors.lastname: Iskra
authors.forename: Nenad
authors.initials: N
authors.lastname: Pandak
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Misetić
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Perić
authors.forename: Davor
authors.initials: D
authors.lastname: Jelaska
authors.forename: Maja
authors.initials: M
authors.lastname: Majetić-Sekovanić
authors.forename: Dragan
authors.initials: D
authors.lastname: Ledina
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Misić-Majerus
authors.forename: Radovan
authors.initials: R
authors.lastname: Radonić
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D017523:Croatia / Q000453:epidemiology; D004196:Disease Outbreaks / Q000706:statistics & numerical data; D005260:Female; D006480:Hemorrhagic Fever with Renal Syndrome / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged