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Clin Infect Dis. 2018 Oct 22. doi: 10.1093/cid/ciy664. [Epub ahead of print]

Potential Role for Urine Polymerase Chain Reaction in the Diagnosis of Whipple's Disease.

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Biofilmcenter and German Consiliary Laboratory for Tropheryma whipplei, German Heart Center Berlin.
Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin.
Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg.
Institute of Medical Microbiology, Virology and Hygiene, University Hospital Hamburg-Eppendorf.
PathoTres Gemeinschaftspraxis für Pathologie, Berlin.
Institute of Pathology, Nephropathology Section, University Hospital Hamburg-Eppendorf.
Medical Department I, Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Germany.



Whipple's disease (WD) is a rare infection with Tropheryma whipplei that is fatal if untreated. Diagnosis is challenging and currently based on invasive sampling. In a case of WD diagnosed from a kidney biopsy, we observed morphologically-intact bacteria within the glomerular capsular space and tubular lumens. This raised the questions of whether renal filtration of bacteria is common in WD and whether polymerase chain reaction (PCR) testing of urine might serve as a diagnostic test for WD.


We prospectively investigated urine samples of 12 newly-diagnosed and 31 treated WD patients by PCR. As controls, we investigated samples from 110 healthy volunteers and patients with excluded WD or acute gastroenteritis.


Out of 12 urine samples from independent, therapy-naive WD patients, 9 were positive for T. whipplei PCR. In 3 patients, fluorescence in situ hybridization visualized T. whipplei in urine. All control samples were negative, including those of 11 healthy carriers with T. whipplei-positive stool samples. In our study, the detection of T. whipplei in the urine of untreated patients correlated in all cases with WD.


T. whipplei is detectable by PCR in the urine of the majority of therapy-naive WD patients. With a low prevalence but far-reaching consequences upon diagnosis, invasive sampling for WD is mandatory and must be based on a strong suspicion. Urine testing could prevent patients from being undiagnosed for years. Urine may serve as a novel, easy-to-obtain specimen for guiding the initial diagnosis of WD, in particular in patients with extra-intestinal WD.

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