The Rise of Tropheryma whipplei: a 12-Year Retrospective Study of PCR Diagnoses in Our Reference Center

Abstract

Tropheryma whipplei is the causative agent of classic Whipple's disease (WD) and other clinical entities, such as localized infection. Asymptomatic carriers have also been reported, mainly based on the testing of fecal samples. Our objective was to undertake a retrospective analysis of molecular biology usage for the diagnosis of WD over a 12-year period in our reference center. We tested 27,923 samples from 15,473 patients. The number of patients tested and the number of patients with a positive PCR result for T. whipplei have increased significantly over the last 12 years (P < 0.0001). Overall, T. whipplei was more frequently recovered from stools (43%), saliva (15%), duodenal biopsy samples (12.5%), blood (5%), and cerebrospinal fluid (CSF) (6%) and less commonly from cardiac valves (3%), urine (0.5%), skin biopsy samples (1%), lymph nodes (2.5%), aqueous humor (0.5%), and intra-articular fluid (1%). Among all the positive samples, we observed that stool samples and skin biopsy samples exhibited a higher prevalence of positivity by real-time quantitative PCR (qPCR) at 10.07% and 15.4%, respectively. The number of patients with a positive PCR result for T. whipplei has increased significantly over the last 12 years, although the positive ratio has not changed. Improvements in diagnostic tools have contributed greatly toward greater knowledge of WD and, consequently, the interest of physicians in this condition. In addition, we propose here an update of the diagnostic strategy for WD when qPCR is being used.

Clinical Manifestations, Treatment, and Diagnosis of Tropheryma whipplei Infections

“…With the introduction of PCR, it became clear that the bacterium could also be found in other samples (18,40). Microscopy of biopsy samples is a costly and invasive method and therefore not frequently used for screening purposes and usually performed only to confirm the diagnosis in the case of a serious suspicion of infection.…”

“…Although most Whipple's disease patients do not present any obvious neurological symptoms, postmortem investigation showed that 90% of brain and spinal cord specimens from both patients and presumed carriers revealed lesions of the CNS, meaning that CNS involvement is more common than expected from the clinical manifestations (33). Another indication for frequent neurological involvement is the presence of T. whipplei DNA in the cerebrospinal fluid (CSF) of patients with classic Whipple's disease even in the absence of evident neurological manifestations (40,130). The prognosis for patients with symptomatic central nervous system involvement remains poor, as major sequelae are seen in 25% of patients and 4-year survival rates are Ͻ75% (131).…”

“…In the early stage, often some of the typical manifestations may be not be present. The presence of the T. whipplei bacterium can be established diagnostically in various tissues and body fluids by several routine methods (40). The different laboratory methods to diagnose T. whipplei infections and the advantages and disadvantages of each diagnostic method will be discussed below.…”

Tropheryma whipplei, a Potential Commensal Detected in Individuals Undergoing Routine Colonoscopy

“…Others, however, have reported a higher prevalence (7.24%) (17). These samples were sent from different countries to be analyzed in a tertiary center for WD, probably because of a suspicion of WD in symptomatic individuals, which may have contributed to this difference.…”

Validation of an rpoB Gene PCR Assay for Detection of Tropheryma whipplei: 10 Years' Experience in a National Reference Laboratory

“…The emergence of real-time PCR technology has substantially improved and facilitated the molecular detection of Tropheryma whipplei, the causative agent of Whipple's disease (2,3). In search of a specific and sensitive PCR protocol, several target genes have already been evaluated, including the 16S rRNA gene (4), the 16S-23S rRNA intergenic spacer region (5), the hsp65 gene (6), and certain repeated sequences (7).…”