title: Insufficient efficacy and safety of intravenous ribavirin in treatment of haemorrhagic fever with renal syndrome caused by Puumala virus.
abstract: BACKGROUND
  Intravenous ribavirin has been reported to be an effective treatment for haemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus in Asia. However, its therapeutic benefits for HFRS caused by Puumala virus (PUUV) in Europe are still unknown.
  
  
  METHODS
  A randomized, open-label study of efficacy and safety of intravenous ribavirin in the treatment of HFRS was conducted in the European part of Russia. Seventy-three patients with suspected HFRS within 4 d of the onset of the disease were randomized to receive either intravenous ribavirin (33 mg/kg, followed by 16 mg/kg given every 6 h for 4 d and by 8 mg/kg given every 8 h for 3 d) plus standard therapy (n = 37) or standard therapy alone (n = 36). The primary outcome was the average change from baseline in viral load over time estimated as area under the viral load curve minus baseline (AUCMB). Fifty-five patients with HFRS confirmed by nested reverse transcriptase - polymerase chain reaction (PCR) assay were included in the assessment of the efficacy. All patients entered into the clinical trial were included in the assessment of the safety.
  
  
  RESULTS
  PUUV was detected in all cases of confirmed HFRS. Viral load kinetics were similar in both treatment groups. Significantly more patients receiving ribavirin than standard therapy experienced low haemoglobin level (95% vs 36%), hyperbilirubinemia (81% vs 3%), sinus bradycardia (43% vs 14%), and rash (19% vs 0%).
  
  
  CONCLUSIONS
  Results of the study showed insufficient efficacy and safety of intravenous ribavirin in the treatment of HFRS caused by PUUV.
authors.affiliation: a Department of Infectious Diseases and Epidemiology , Izhevsk State Medical Academy , Izhevsk , Russia.
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Malinin
authors.affiliation: b Laboratory for Zoonoses , Central Research Institute of Epidemiology , Moscow , Russia.
authors.forename: Alexander E
authors.initials: AE
authors.lastname: Platonov
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006480:Hemorrhagic Fever with Renal Syndrome / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D029262:Puumala virus / Q000302:isolation & purification*; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects*; D012426:Russia; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D012254:Ribavirin
keywords: Haemorrhagic fever with renal syndrome; Puumala virus; ribavirin