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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 \u201c<jats:italic>Tropheryma whippelli<\/jats:italic>.\u201d 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, \u201c<jats:italic>T. whippelii<\/jats:italic>\u201d 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 \u201c<jats:italic>T. whippelii<\/jats:italic>\u201d that might account for the variable clinical manifestations. So far, six different \u201c<jats:italic>T. whippelii<\/jats:italic>\u201d subtypes have been found by analysis of their 16S-23S rDNA spacer region. Further studies of the pathogen \u201c<jats:italic>T. whippelii<\/jats:italic>\u201d 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.<\/jats:p><\/jats:sec>","DOI":"10.1128\/cmr.14.3.561-583.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:58:35Z","timestamp":1027763915000},"page":"561-583","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":223,"title":["Whipple's Disease and \u201c<i>Tropheryma whippelii<\/i>\u201d"],"prefix":"10.1128","volume":"14","author":[{"given":"Fabrizio","family":"Dutly","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Medical Microbiology, University of Zu\u0308rich, CH-8028 Zu\u0308rich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Altwegg","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Medical Microbiology, University of Zu\u0308rich, CH-8028 Zu\u0308rich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410210121"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-76-3-112-6-467"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/516941"},{"key":"e_1_3_2_5_2","first-page":"221","article-title":"Lymphangiectasis intestini.","volume":"46","author":"Allchin W. 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