title: Severe leptospirosis complicated by Epstein-Barr Virus reactivation.
abstract: BACKGROUND
  Weil's disease is a severe, potentially fatal illness following Leptospira interrogans infection. The reported case of a patient suffering from acute renal failure, jaundice, thrombocytopenia, rhabdomyolysis and encephalitis syndrome highlights the clinical challenge in reference to Weil syndrome complicated by Epstein-Barr Virus (EBV) reactivation.
  
  
  METHODS
  The diagnosis of leptospirosis was performed using four different diagnostic methods. Sera were analyzed with an in-house IgM and IgG enzyme-linked immunosorbent assay (ELISA) and indirect haemagglutination assay (IHA). Microscopic agglutination test (MAT) was done using 17 reference strains comprising 14 serogroups and 17 serovars. Polyvalent EBV-IgG analysis, EBV-IgG/IgM/IgA western blot analysis as well as quantitative EBV polymerase chain reaction (PCR) were performed.
  
  
  RESULTS
  Leptospira IHA showed an initial titer of 1:640 (cut-off 1:320), leptospiral IgG was negative, but IgM was positive. MAT was negative at that time for all 17 strains analyzed. One week later, leptospirosis IHA titer increased to 1:20,480. Leptospiral IgG was now positive, -IgM remained positive and urine was tested negative for leptospiral DNA. The MAT showed positive results for L. interrogans serovar Bataviae, serovar Copenhageni, serovar Pyrogenes and L. borgpetersenii serovar Serjoe. During follow-up examinations, both the leptospiral IgM and IgG remained positive and MAT showed positive results for L. interrogans of different serovars. EBV IgA immunoblot taken at admission was positive for VCA-p18, quantitative EBV-PCR showed an EBV viral load of 2.8E3 copies/ml indicating acute EBV-reactivation.
  
  
  CONCLUSIONS
  Leptospirosis represents a neglected and re-emerging disease which is difficult to diagnose since Leptospira-PCR from whole blood or urine is frequently negative in the case of early empiric antibiotic treatment. EBV-reactivation might represent a severe complication in Weil's disease which potentially aggravates clinical manifestations of leptospirosis including hepatitis, nephritis, and rhabdomyolysis. Thus, there might be a need for peripheral blood EBV-PCR and EBV blotting in patients suffering from complicated Weil syndrome, also in terms of the choice of antibiotic treatment.
authors.affiliation: Institute of Medical Microbiology, University Hospital of Friedrich-Schiller-University Jena, Erlanger Allee 101, 07743, Jena, Germany. matthias.karrasch@med.uni-jena.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Karrasch
authors.affiliation: Department of Internal Medicine III (Nephrology), University Hospital of Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Herfurth
authors.affiliation: Institute of Diagnostic and Interventional Radiology, University Hospital of Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Kläver
authors.affiliation: Department of Internal Medicine II (Hematology/Oncology), University Hospital of Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Miethke
authors.affiliation: German Consiliary Laboratory for Leptospirosis, Federal Institute for Risk Assessment, Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Mayer-Scholl
authors.affiliation: German Consiliary Laboratory for Leptospirosis, Federal Institute for Risk Assessment, Berlin, Germany.
authors.forename: Enno
authors.initials: E
authors.lastname: Luge
authors.affiliation: Institute of Medical Microbiology, University Hospital of Friedrich-Schiller-University Jena, Erlanger Allee 101, 07743, Jena, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Straube
authors.affiliation: Department of Internal Medicine III (Nephrology), University Hospital of Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Busch
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D015153:Blotting, Western; D004279:DNA, Viral / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis* / Q000473:pathology*; D006386:Hemagglutination Tests; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007922:Leptospirosis / Q000150:complications / Q000175:diagnosis* / Q000473:pathology*; D008297:Male; D016133:Polymerase Chain Reaction; D014775:Virus Activation
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D004279:DNA, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M