title: Instructive even after a decade: Complete results of initial virological diagnostics and re-evaluation of molecular data in the German rabies virus "outbreak" caused by transplantations.
abstract: In 2005, six patients in Germany received solid organs and both corneas from a donor with an unrecognized rabies infection. Initial virological diagnostics with the machinery available at the two national reference laboratories could quickly clarify the situation. Rabies virus antigen was detected in the organ donor's brain. In two of the three recipients with neurological alterations, intra vitam diagnosis was achieved by conventional RT-PCRs. Comparison of the phylogenetic relatedness of the different viral isolates proved transmission from the donor and, consequently, also established the diagnosis for the third patient. As indicated by the titre of neutralizing antibodies, the liver transplant recipient was protected from the lethal infection due to a vaccination against rabies virus, which he had received more than 15 years ago. All samples from the recipients of the corneas were invariably negative. Re-evaluation of the molecular data by real-time PCR did not lead to an improvement of intra vitam diagnosis but provided intriguing insights regarding the relative amounts of rabies virus RNA in different body fluids and peripheral organs. In saliva and skin, they were 250-200,000 times lower than in the infected patient's brains. Furthermore, in saliva samples taken serially from the same patient fluctuations by a factor of 160-500 were recorded. These findings highlight the problems of intra vitam diagnosis of rabies virus infections and make understandable why the virus can escape from all diagnostic attempts. Finally, in this context one should recall an almost trivial fact: Simple and appropriate postexposure prophylaxis could not only have saved the young organ donor's life but would also have prevented the whole transplantation-associated rabies "outbreak" in Germany.
authors.affiliation: Institute of Virology, National Consiliary Laboratory for Rabies, Essen University Hospital, University of Duisburg-Essen, Hufelandstr., D-45122 Essen, Germany. Electronic address: stefan.ross@uni-due.de.
authors.forename: R Stefan
authors.initials: RS
authors.lastname: Ross
authors.affiliation: Institute of Virology, National Consiliary Laboratory for Rabies, Essen University Hospital, University of Duisburg-Essen, Hufelandstr., D-45122 Essen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Wolters
authors.affiliation: Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Diagnostic Virology, Südufer 10, D-17493 Greifswald-Insel Riems, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Hoffmann
authors.affiliation: Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Molecular Pathogenesis, Naumburger Str. 96 a, 07743 Jena, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Geue
authors.affiliation: Institute of Virology, National Consiliary Laboratory for Rabies, Essen University Hospital, University of Duisburg-Essen, Hufelandstr., D-45122 Essen, Germany.
authors.forename: Sergei
authors.initials: S
authors.lastname: Viazov
authors.affiliation: Institute of Virology, National Consiliary Laboratory for Rabies, Essen University Hospital, University of Duisburg-Essen, Hufelandstr., D-45122 Essen, Germany.
authors.forename: Nico
authors.initials: N
authors.lastname: Grüner
authors.affiliation: Institute of Virology, National Consiliary Laboratory for Rabies, Essen University Hospital, University of Duisburg-Essen, Hufelandstr., D-45122 Essen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roggendorf
authors.affiliation: Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, WHO Collaborating Centre for Rabies Surveillance and Research, OIE and National Reference Laboratory for Rabies, Südufer 10, D-17493 Greifswald-Insel Riems, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000821:virology; D004196:Disease Outbreaks; D005260:Female; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D011818:Rabies / Q000453:epidemiology* / Q000635:transmission*; D011820:Rabies virus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D012463:Saliva / Q000821:virology; D012867:Skin / Q000821:virology; D014180:Transplantation / Q000009:adverse effects*; D019562:Viral Load
keywords: Cellular immune response; Cornea grafting; Organ transplantation; Phylogenetic analysis; Rabies virus; Real-time PCR; Tissue culture; Transmission