Whipple's Disease and “Tropheryma whippelii”

Abstract

SUMMARY Whipple's disease is a rare bacterial infection that may involve any organ system in the body. It occurs primarily in Caucasian males older than 40 years. The gastrointestinal tract is the most frequently involved organ, with manifestations such as abdominal pain, malabsorption syndrome with diarrhea, and weight loss. Other signs include low-grade fever, lymphadenopathy, skin hyperpigmentation, endocarditis, pleuritis, seronegative arthritis, uveitis, spondylodiscitis, and neurological manifestations, and these signs may occur in the absence of gastrointestinal manifestations. Due to the wide variability of manifestations, clinical diagnosis is very difficult and is often made only years or even decades after the initial symptoms have appeared. Trimethoprim-sulfamethoxazole for at least 1 year is usually considered adequate to eradicate the infection. The microbiological diagnosis of this insidious disease is rendered difficult by the virtual lack of culture and serodiagnostic methods. It is usually based on the demonstration of periodic acid-Schiff-positive particles in infected tissues and/or the presence of bacteria with an unusual trilaminar cell wall ultrastructure by electron microscopy. Recently, the Whipple bacteria have been characterized at the molecular level by amplification of their 16S rRNA gene(s). Phylogenetic analysis of these sequences revealed a new bacterial species related to the actinomycete branch which was named “Tropheryma whippelli.” Based on its unique 16S ribosomal DNA (rDNA) sequence, species-specific primers were selected for the detection of the organism in clinical specimens by PCR. This technique is currently used as one of the standard methods for establishing the diagnosis of Whipple's disease. Specific and broad-spectrum PCR amplifications mainly but not exclusively from extraintestinal specimens have significantly improved diagnosis, being more sensitive than histopathologic analysis. However, “T. whippelii” DNA has also been found in persons without clinical and histological evidence of Whipple's disease. It is unclear whether these patients are true asymptomatic carriers or whether differences in virulence exist among strains of “T. whippelii” that might account for the variable clinical manifestations. So far, six different “T. whippelii” subtypes have been found by analysis of their 16S-23S rDNA spacer region. Further studies of the pathogen “T. whippelii” as well as the host immune response are needed to fully understand this fascinating disease. The recent cultivation of the organisms is a promising major step in this direction.

Looking for Tropheryma whipplei Source and Reservoir in Rural Senegal

“…For several reasons, it has been speculated for a long time that T. whipplei has an environmental source: the presence of DNA of the bacterium in sewage samples 24 ; the phylogenetic relatedness of T. whipplei to Actinomycetes, which are essentially environmental microorganisms, especially from soil but also from freshwater and seawater sediments 25 ; and the high proportion of farmers among the first reported patients, which suggested exposure to soil as one possible route of infection. 25 The presence of T. whipplei in sewage plants may suggest a possible environmental reservoir of the bacterium, but may simply result from excretion of the bacterium from the stool specimens of patients and carriers.…”

The prevalence of Tropheryma whippelii DNA in saliva from healthy controls and patients with spondyloarthropathy

“…Although the prominent symptoms are diarrhea, malabsorption, and weight loss, the arthritis may precede the gastrointestinal symptoms [1]. Furthermore, some cases of WD shows the clinical manifestations of spondyloarthropathy (SpA), such as oligoarthritis pattern, axial involvement, sacroiliitis, and association with HLA-B27 [2].…”

“…The presence of periodic acid-SchiV-staining foamy macrophages in the lamina propria of duodenum is diagnostic of WD [1]. Recently the molecular diagnosis using TW-speciWc gene ampliWcation is promising.…”

“…Although the prominent symptoms are diarrhea, malabsorption, and weight loss, the arthritis may precede the gastrointestinal symptoms [1]. Furthermore, some cases of WD shows the clinical manifestations of spondyloarthropathy (SpA), such as oligoarthritis pattern, axial involvement, sacroiliitis, and association with HLA-B27 [2].The presence of periodic acid-SchiV-staining foamy macrophages in the lamina propria of duodenum is diagnostic of WD [1]. Recently the molecular diagnosis using TW-speciWc gene ampliWcation is promising.…”

Microflora in Crohn’s disease: the emergence of adherent and invasiveEscherichia coli

“…GCB has features in common with UC (macroscopic appearance, regional distribution and immunopathology), Whipple's disease (PAS-positive macrophages) and CD (granulomatous inflammation, bacteria within macrophages and may respond to fluroquinolones) in humans but it is not identical to any of these disease syndromes [46][47][48][49]. 16S rDNA libraries generated from GCB dogs are dominated by sequences for Enterobacteriaceae, predominantly E. coli and Shigella and FISH probes recognize invasive E. coli within the colonic mucosa (in the lamina propria and macrophages) of Boxer dogs with GCB but not unaffected controls, and non-GCB colitis.…”