title: Detection of Puumala hantavirus antigen in human intestine during acute hantavirus infection.
abstract: BACKGROUND
  Puumala virus (PUUV) is the most important hantavirus species in Central Europe. Nephropathia epidemica (NE), caused by PUUV, is characterized by acute renal injury (AKI) with thrombocytopenia and frequently gastrointestinal symptoms.
  
  
  METHODS
  456 patients with serologically and clinically confirmed NE were investigated at time of follow-up in a single clinic. The course of the NE was investigated using medical reports. We identified patients who had endoscopy with intestinal biopsy during acute phase of NE. Histopathological, immunohistochemical and molecular analyses of the biopsies were performed.
  
  
  RESULTS
  Thirteen patients underwent colonoscopy or gastroscopy for abdominal pain, diarrhea, nausea and vomiting during acute phase of NE. Immunohistochemistry (IHC) revealed PUUV nucleocapsid antigen in 11 biopsies from 8 patients; 14 biopsies from 5 patients were negative for PUUV nucleocapsid antigen. IHC localized PUUV nucleocapsid antigen in endothelial cells of capillaries or larger vessels in the lamina propria. Rate of AKI was not higher and severity of AKI was not different in the PUUV-positive compared to the PUUV-negative group. All IHC positive biopsies were positive for PUUV RNA using RT-PCR. Phylogenetic reconstruction revealed clustering of all PUUV strains from this study with viruses previously detected from the South-West of Germany. Long-term outcome was favorable in both groups.
  
  
  CONCLUSIONS
  In patients with NE, PUUV nucleocapsid antigen and PUUV RNA was detected frequently in the intestine. This finding could explain frequent GI-symptoms in NE patients, thus demonstration of a more generalized PUUV infection. The RT-PCR was an effective and sensitive method to detect PUUV RNA in FFPE tissues. Therefore, it can be used as a diagnostic and phylogenetic approach also for archival materials. AKI was not more often present in patients with PUUV-positive IHC. This last finding should be investigated in larger numbers of patients with PUUV infection.
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Robert-Bosch Hospital, Auerbachstrasse 110, Stuttgart, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Latus
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, WHO Collaborating Centre for Arbovirus and Haemmorrhagic Fever Reference and Research, Bernhard-Nocht-Strasse 74, Hamburg, Germany.
authors.forename: Klara
authors.initials: K
authors.lastname: Tenner-Racz
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, WHO Collaborating Centre for Arbovirus and Haemmorrhagic Fever Reference and Research, Bernhard-Nocht-Strasse 74, Hamburg, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Racz
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Robert-Bosch Hospital, Auerbachstrasse 110, Stuttgart, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kitterer
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, WHO Collaborating Centre for Arbovirus and Haemmorrhagic Fever Reference and Research, Bernhard-Nocht-Strasse 74, Hamburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cadar
authors.affiliation: Department of Diagnostic Medicine, Division of Pathology, Robert-Bosch Hospital, Auerbachstrasse 110, Stuttgart, Germany.
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Robert-Bosch Hospital, Auerbachstrasse 110, Stuttgart, Germany.
authors.forename: M Dominik
authors.initials: MD
authors.lastname: Alscher
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, WHO Collaborating Centre for Arbovirus and Haemmorrhagic Fever Reference and Research, Bernhard-Nocht-Strasse 74, Hamburg, Germany; German Centre for Infection Research (DZIF), partner site Hamburg-Luebeck-Borstel, Hamburg, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Schmidt-Chanasit
authors.affiliation: Department of Internal Medicine, Division of Nephrology, Robert-Bosch Hospital, Auerbachstrasse 110, Stuttgart, Germany.
authors.forename: Niko
authors.initials: N
authors.lastname: Braun
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology*; D001706:Biopsy; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D006480:Hemorrhagic Fever with Renal Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007422:Intestines / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D019251:Nucleocapsid / Q000235:genetics / Q000276:immunology; D029262:Puumala virus / Q000235:genetics / Q000276:immunology*; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000956:Antigens, Viral; D012367:RNA, Viral