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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
['Moter|Annette|A|', 'Janneck|Matthias|M|', 'Wolters|Manuel|M|', 'Iking-Konert|Christof|C|', 'Wiessner|Alexandra|A|', 'Loddenkemper|Christoph|C|', 'Hartleben|Björn|B|', 'Lütgehetmann|Marc|M|', 'Schmidt|Julia|J|', 'Langbehn|Ulrike|U|', 'Janssen|Sabrina|S|', 'Geelhaar-Karsch|Anika|A|', 'Schneider|Thomas|T|', 'Moos|Verena|V|', 'Rohde|Holger|H|', 'Kikhney|Judith|J|', 'Wiech|Thorsten|T|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D006801:Humans D008297:Male D008875:Middle Aged D025202:Molecular Diagnostic Techniques D016133:Polymerase Chain Reaction D011446:Prospective Studies D054851:Tropheryma D014556:Urine D008061:Whipple Disease D055815:Young Adult
Tropheryma whipplei fluorescence in situ hybridization Whipple’s disease electron microscopy real-time PCR