PURPOSE OF REVIEW: The availability of and advantages in molecular technology and immunology have led to an improved understanding of the etiology and pathogenesis of Whipple disease. As this rare infection represents a model disease reflecting the input of novel findings into clinical medicine and therapy, this review intends to highlight newer findings and put them in context. RECENT FINDINGS: Sequencing of 16S rRNA allowed the phylogeny of the bacterium to be determined. The culture and subsequent genome analysis have led to improved diagnosis and monitoring of the disease, for example by PCR or immunohistochemistry. New experimental approaches hint of defects in T-cell and macrophage immunity in patients. Antibiotic therapy will soon be based on data from the first prospective therapy study. SUMMARY: Within a few years the findings from molecular genetics and immunology as well as concerted research activities from the European Consortium on Whipple Disease which established a data and material bank could be translated into clinical medicine. Thus, for patients with Whipple disease an improved basis for diagnosis and therapy have been achieved.

Whipple's disease: new aspects of pathogenesis and treatment.Lancet Infect Dis. 2008 Mar;8(3):179-90.

100 years after its first description by George H Whipple, the diagnosis and treatment of Whipple's disease is still a subject of controversy. Whipple's disease is a chronic multisystemic disease. The infection is very rare, although the causative bacterium, Tropheryma whipplei, is ubiquitously present in the environment. We review the epidemiology of Whipple's disease and the recent progress made in the understanding of its pathogenesis and the biology of its agent. The clinical features of Whipple's disease are non-specific and sensitive diagnostic methods such as PCR with sequencing of the amplification products and immunohistochemistry to detect T whipplei are still not widely distributed. The best course of treatment is not completely defined, especially in relapsing disease, neurological manifestations, and in cases of immunoreconstitution after initiation of antibiotic treatment. Patients without the classic symptoms of gastrointestinal disease might be misdiagnosed or insufficiently treated, resulting in a potentially fatal outcome or irreversible neurological damage. Thus, we suggest procedures for the improvement of diagnosis and an optimum therapeutic strategy.

Advances in Tropheryma whipplei research: the rush to find biomarkers for Whipple's disease.Future Microbiol. 2007 Dec;2:631-42.

Whipple's disease (WD) is a systemic chronic infection, caused by the Gram-positive bacterium Tropheryma whipplei. There are several clinical traits linked to WD: histological lesions in the GI tract in association with diverse clinical manifestations (classic WD), endocarditis with negative blood cultures, and isolated neurological infection. WD is rare, predominantly affects middle-aged men and is fatal without treatment. The most recent strategy for diagnosing WD uses the results of diastase-resistant periodic acid Schiff staining and PCR in parallel, both performed on involved organ/tissue biopsy (small intestine, cardiac valve and cerebrospinal fluid). The generation of rabbit polyclonal antibodies has enabled the detection of the bacterium in tissues by immunohistochemical staining. However, the diagnosis of WD remains an invasive procedure. The recent achievement of stable bacterial culture and sequencing of the T. whipplei genome has opened a framework for the development of a biomarker platform. Several studies in different fields have been performed, for example, transcriptomics, immunoproteomics and comparative proteomics. Biomarker candidates have been proposed for the development of less invasive procedures for diagnosing WD.