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      Tropheryma whipplei in Patients with Pneumonia

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          Abstract

          This bacterium may be an etiologic agent of pneumonia.

          Abstract

          Tropheryma whipplei is the etiologic pathogenic agent of Whipple disease (WD), characterized by various clinical signs, such as diarrhea, weight loss, lymphadenopathy, and polyarthritis. PCR-based methods for diagnosis of WD have been developed. T. whipplei has been identified in saliva and stool samples from patients with WD and from healthy persons. T. whipplei DNA has also been found in bronchoalveolar lavage (BAL) samples of a child with pneumonia. We detected DNA of T. whipplei in 6 (3%) of 210 BAL samples collected in intensive care units by using 16S rDNA and specific quantitative PCR. We identified 4 novel genotypes of T. whipplei. In 1 case, T. whipplei was the only bacterium; in 4 others, it was associated with buccal flora. We suggest that T. whipplei should be investigated as an etiologic agent of pneumonia.

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          Most cited references25

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          Identification of the uncultured bacillus of Whipple's disease.

          Whipple's disease is a systemic disorder known for 85 years to be associated with an uncultured, and therefore unidentified, bacillus. We used a molecular genetic approach to identify this organism. The bacterial 16S ribosomal RNA (rRNA) sequence was amplified directly from tissues of five unrelated patients with Whipple's disease by means of the polymerase chain reaction, first with broad-range primers and then with specific primers. We determined and analyzed the nucleotide sequence of the amplification products. A unique 1321-base bacterial 16S rRNA sequence was amplified from duodenal tissue of one patient. This sequence indicated the presence of a previously uncharacterized organism. We then detected this sequence in tissues from all 5 patients with Whipple's disease, but in none of those from 10 patients without the disorder. According to phylogenetic analysis, this bacterium is a gram-positive actinomycete that is not closely related to any known genus. We have identified the uncultured bacillus associated with Whipple's disease. The phylogenetic relations of this bacterium, its distinct morphologic characteristics, and the unusual features of the disease are sufficient grounds for naming this bacillus Tropheryma whippelii gen. nov. sp. nov. Our findings also provide a basis for a specific diagnostic test for this organism.
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            Whipple's disease.

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              Cultivation of the bacillus of Whipple's disease.

              Whipple's disease is a systemic bacterial infection, but to date no isolate of the bacterium has been established in subculture, and no strain of this bacterium has been available for study. Using specimens from the aortic [corrected] valve of a patient with endocarditis due to Whipple's disease, we isolated and propagated a bacterium by inoculation in a human fibroblast cell line (HEL) with the use of a shell-vial assay. We tested serum samples from our patient, other patients with Whipple's disease, and control subjects for the presence of antibodies to this bacterium. The bacterium of Whipple's disease was grown successfully in HEL cells, and we established subcultures of the isolate. Indirect immunofluorescence assays showed that the patient's serum reacted specifically against the bacterium. Seven of 9 serum samples from patients with Whipple's disease had IgM antibody titers of 1:50 or more, as compared with 3 of 40 samples from the control subjects (P<0.001). Polyclonal antibodies against the bacterium were generated by inoculation of the microorganism into mice and were used to detect bacteria in the excised cardiac tissue from our patient on immunohistochemical analysis. The 16S ribosomal RNA gene of the cultured bacterium was identical to the sequence for Tropheryma whippelii identified previously in tissue samples from patients with Whipple's disease. The strain we have grown is available in the French National Collection. We cultivated the bacterium of Whipple's disease, detected specific antibodies in tissue from the source patient, and generated specific antibodies in mice to be used in the immunodetection of the microorganism in tissues. The development of a serologic test for Whipple's disease may now be possible.
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                Author and article information

                Journal
                Emerg Infect Dis
                EID
                Emerging Infectious Diseases
                Centers for Disease Control and Prevention
                1080-6040
                1080-6059
                February 2010
                : 16
                : 2
                : 258-263
                Affiliations
                [1]CNRS-IRD Faculté de Médecine, Marseille, France (S. Bousbia, L. Papazian, F. Fenollar, W. Li, B. La Scola, D. Raoult)
                [2]Hôpitaux Sud, Marseille (L. Papazian, J.P. Auffray, L. Chiche)
                [3]Hôpital Nord, Marseille (C. Martin)
                Author notes
                Address for correspondence: Didier Raoult, Université de la Méditerranée – Faculte de Medecine (URMITE), CNRS UMR6236 IDR 198, Centre National de Reference, Marseille, France; email: didier.raoult@ 123456gmail.com
                Article
                09-0610
                10.3201/eid1602.090610
                2957999
                20113556
                dd0d9788-8378-4413-92de-ae3faa027ef1
                History
                Categories
                Research

                Infectious disease & Microbiology
                bacteria,research,whipple disease diagnosis,tropheryma whipplei,genotyping,whipple disease,ventilator-associated pneumonia

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