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Citation: GeißdÖrfer W, Moter A, Bogdan C. .
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Image of FIGURE 1

PAS staining of a duodenal biopsy specimen shows lymphangiectasia and massive infiltration of the lamina propria by strongly PAS-positive foamy macrophages containing (image kindly provided by Christoph Loddenkemper, Pathotres, Berlin, Germany). doi:10.1128/9781555817381.ch67.f1

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Image of FIGURE 2

FISH of a duodenal biopsy of an untreated Whipple’s disease patient using a -specific probe ( ). The low-magnification image shows clusters of cells (yellow) against the slightly greenish autofluorescent background of the tissue. Host cell nuclei are stained blue with 4′, 6-diamidino-2-phenylindole (DAPI). Inset shows single bacteria at a higher magnification. doi:10.1128/9781555817381.ch67.f2

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Image of FIGURE 3

FISH of a heart valve section in a case of culture-negative endocarditis using a -specific probe (Cy3, orange) ( ). The low-magnification image shows extensive areas with bacterial colonization (slightly orange glimmer) along with calcified tissue (bright yellow-green autofluorescence). Host cell nuclei are stained blue with 4′,6-diamidino-2-phenylindole (DAPI). Inset shows dense clusters of cells at a higher magnification (orange). doi:10.1128/9781555817381.ch67.f3

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Hierarchical scheme for the diagnosis of Whipple’s disease (modified from and ). 1, positive PCR should be confirmed by 16S rRNA gene sequencing or a second specific PCR detecting a different target sequence; 2, IHC and FISH are available only in specialized laboratories. doi:10.1128/9781555817381.ch67.f4

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1. Fenollar F,, Puechal X,, Raoult D. 2007. Whipple’s disease. N Engl J Med 356:5566.
2. Keita AK,, Raoult D,, Fenollar F. 2013. Tropheryma whipplei as a commensal bacterium. Future Microbiol 8:5771.
3. Moos V,, Schneider T. 2011. Changing paradigms in Whipple’s disease and infection with Tropheryma whipplei. Eur J Clin Microbiol Infect Dis 30:11511158.
4. Schneider T,, Moos V,, Loddenkemper C,, Marth T,, Fenollar F,, Raoult D. 2008. Whipple’s disease: new aspects of pathogenesis and treatment. Lancet Infect Dis 8:179190.
5. Wilson KH,, Blitchington R,, Frothingham R,, Wilson JA. 1991. Phylogeny of the Whipple’s-disease-associated bacterium. Lancet 338:474475.
6. La Scola B,, Fenollar F,, Fournier PE,, Altwegg M,, Mallet MN,, Raoult D. 2001. Description of Tropheryma whipplei gen. nov., sp. nov., the Whipple’s disease bacillus. Int J Syst Evol Microbiol 51:14711479.
7. Bentley SD,, Maiwald M,, Murphy LD,, Pallen MJ,, Yeats CA,, Dover LG,, Norbertczak HT,, Besra GS,, Quail MA,, Harris DE,, von Herbay A,, Goble A,, Rutter S,, Squares R,, Squares S,, Barrell BG,, Parkhill J,, Relman DA. 2003. Sequencing and analysis of the genome of the Whipple’s disease bacterium Tropheryma whipplei. Lancet 361:637644.
8. Raoult D,, Birg ML,, La Scola B,, Fournier PE,, Enea M,, Lepidi H,, Roux V,, Piette JC,, Vandenesch F,, VitalDurand D,, Marrie TJ. 2000. Cultivation of the bacillus of Whipple’s disease. N Engl J Med 342:620625.
9. Silva MT,, Macedo PM,, Moura Nunes JF. 1985. Ultrastructure of bacilli and the bacillary origin of the macrophagic inclusions in Whipple’s disease. J Gen Microbiol 131:10011013.
10. Schoedon G,, Goldenberger D,, Forrer R,, Gunz A,, Dutly F,, Hochli M,, Altwegg M,, Schaffner A. 1997. Deactivation of macrophages with interleukin-4 is the key to the isolation of Tropheryma whippelii. J Infect Dis 176:672677.
11. Fenollar F,, Birg ML,, Gauduchon V,, Raoult D. 2003. Culture of Tropheryma whipplei from human samples: a 3-year experience (1999 to 2002). J Clin Microbiol 41:38163822.
12. Puechal X,, Fenollar F,, Raoult D. 2007. Cultivation of Tropheryma whipplei from the synovial fluid in Whipple’s arthritis. Arthritis Rheum 56:17131718.
13. Drancourt M,, Raoult D,, Lepidi H,, Fenollar F,, Birg ML,, Bodaghi B,, Hoang PL,, Lelievre JD. 2003. Culture of Tropheryma whippelii from the vitreous fluid of a patient presenting with unilateral uveitis. Ann Intern Med 139: 10461047.
14. Angelakis E,, Fenollar F,, Lepidi H,, Birg ML,, Raoult D. 2010. Tropheryma whipplei in the skin of patients with classic Whipple’s disease. J Infect 61:266269.
15. La Scola B,, Fenollar F,, Perreal C,, Raoult D. 2011. Epidemiologic implications of the first isolation and cultivation of Tropheryma whipplei from a saliva sample. Ann Intern Med 154:443444.
16. Raoult D,, Fenollar F,, Birg ML. 2006. Culture of T. whipplei from the stool of a patient with Whipple’s disease. N Engl J Med 355:15031505.
17. Renesto P,, Crapoulet N,, Ogata H,, La Scola B,, Vestris G,, Claverie JM,, Raoult D. 2003. Genome-based design of a cell-free culture medium for Tropheryma whipplei. Lancet 362:447449.
18. Lagier JC,, Lepidi H,, Raoult D,, Fenollar F. 2010. Systemic Tropheryma whipplei: clinical presentation of 142 patients with infections diagnosed or confirmed in a reference center. Medicine 89:337345.
19. Maiwald M,, Schuhmacher F,, Ditton HJ,, von Herbay A. 1998. Environmental occurrence of the Whipple’s disease bacterium (Tropheryma whippelii). Appl Environ Microbiol 64:760762.
20. Schöniger-Hekele M,, Petermann D,, Weber B,, Müller C. 2007. Tropheryma whipplei in the environment: survey of sewage plant influxes and sewage plant workers. Appl Environ Microbiol 73:20332035.
21. Fenollar F,, Keita AK,, Buffet S,, Raoult D. 2012. Intrafamilial circulation of Tropheryma whipplei, France. Emerg Infect Dis 18:949955.
22. Moos V,, Schneider T. 2012. The role of T cells in the pathogenesis of classical Whipple’s disease. Expert Rev Anti Infect Ther 10:253255.
23. Ghigo E,, Capo C,, Aurouze M,, Tung CH,, Gorvel JP,, Raoult D,, Mege JL. 2002. Survival of Tropheryma whipplei, the agent of Whipple’s disease, requires phagosome acidification. Infect Immun 70:15011506.
24. Schinnerling K,, Moos V,, Geelhaar A,, Allers K,, Loddenkemper C,, Friebel J,, Conrad K,, Kuhl AA,, Erben U,, Schneider T. 2011. Regulatory T cells in patients with Whipple’s disease. J Immunol 187:40614067.
25. Geelhaar A,, Moos V,, Schinnerling K,, Allers K,, Loddenkemper C,, Fenollar F,, LaScola B,, Raoult D,, Schneider T. 2010. Specific and nonspecific B-cell function in the small intestines of patients with Whipple’s disease. Infect Immun 78:45894592.
26. Compain C,, Sacre K,, Puechal X,, Klein I,, Vital-Durand D,, Houeto JL,, De Broucker T,, Raoult D,, Papo T. 2013. Central nervous system involvement in Whipple disease: clinical study of 18 patients and long-term follow-up. Medicine 92:324330.
27. Dobbins WO. 1987. Whipple’s Disease. Charles C. Thomas, Springfield, IL.
28. Schoenberger SD,, Thinda S,, Kim SJ. 2012. Tropheryma whipplei crystalline keratopathy: report of a case and updated review of the literature. Case Rep Ophthalomol Med 2012:707898.
29. Touitou V,, Fenollar F,, Cassoux N,, Merle-Beral H,, Le Hoang P,, Amoura Z,, Drancourt M,, Bodaghi B. 2012. Ocular Whipple’s disease: therapeutic strategy and long-term follow-up. Ophthalmology 119:14651469.
30. Fenollar F,, Celard M,, Lagier JC,, Lepidi H,, Fournier PE,, Raoult D. 2013. Tropheryma whipplei endocarditis. Emerg Infect Dis 19:17211730.
31. Geißdörfer W,, Moos V,, Moter A,, Loddenkemper C,, Jansen A,, Tandler R,, Morguet AJ,, Fenollar F,, Raoult D,, Bogdan C,, Schneider T. 2012. High frequency of Tropheryma whipplei in culture-negative endocarditis. J Clin Microbiol 50:216222.
32. Schaller J,, Carlson JA. 2009. Erythema nodosum-like lesions in treated Whipple’s disease: signs of immune reconstitution inflammatory syndrome. J Am Acad Dermatol 60:277288.
33. Moos V,, Feurle GE,, Schinnerling K,, Geelhaar A,, Friebel J,, Allers K,, Moter A,, Kikhney J,, Loddenkemper C,, Kuhl AA,, Erben U,, Fenollar F,, Raoult D,, Schneider T. 2013. Immunopathology of immune reconstitution inflammatory syndrome in Whipple’s disease. J Immunol 190:23542361.
34. Raoult D,, Fenollar F,, Rolain JM,, Minodier P,, Bosdure E,, Li W,, Garnier JM,, Richet H. 2010. Tropheryma whipplei in children with gastroenteritis. Emerg Infect Dis 16:776782.
35. Edouard S,, Fenollar F,, Raoult D. 2012. The rise of Tropheryma whipplei: a 12-year retrospective study of PCR diagnoses in our reference center. J Clin Microbiol 50:39173920.
36. Urbanski G,, Rivereau P,, Artru L,, Fenollar F,, Raoult D,, Puechal X. 2012. Whipple disease revealed by lung involvement: a case report and literature review. Chest 141:15951598.
37. Lozupone C,, Cota-Gomez A,, Palmer BE,, Linderman DJ,, Charlson ES,, Sodergren E,, Mitreva M,, Abubucker S,, Martin J,, Yao G,, Campbell TB,, Flores SC,, Ackerman G,, Stombaugh J,, Ursell L,, Beck JM,, Curtis JL,, Young VB,, Lynch SV,, Huang L,, Weinstock GM,, Knox KS,, Twigg H,, Morris A,, Ghedin E,, Bushman FD,, Collman RG,, Knight R,, Fontenot AP. 2013. Widespread colonization of the lung by Tropheryma whipplei in HIV infection. Am J Respir Crit Care Med 187:11101117.
38. Rolain JM,, Fenollar F,, Raoult D. 2007. False positive PCR detection of Tropheryma whipplei in the saliva of healthy people. BMC Microbiol 7:48.
39. Fenollar F,, Laouira S,, Lepidi H,, Rolain JM,, Raoult D. 2008. Value of Tropheryma whipplei quantitative polymerase chain reaction assay for the diagnosis of Whipple disease: usefulness of saliva and stool specimens for first-line screening. Clin Infect Dis 47:659667.
40. Fenollar F,, Trani M,, Davoust B,, Salle B,, Birg ML,, Rolain JM,, Raoult D. 2008. Prevalence of asymptomatic Tropheryma whipplei carriage among humans and nonhuman primates. J Infect Dis 197:880887.
41. Keita AK,, Brouqui P,, Badiaga S,, Benkouiten S,, Ratmanov P,, Raoult D,, Fenollar F. 2013. Tropheryma whipplei prevalence strongly suggests human transmission in homeless shelters. Int J Infect Dis 17:12.
42. Keita AK,, Mediannikov O,, Ratmanov P,, Diatta G,, Bassene H,, Roucher C,, Tall A,, Sokhna C,, Trape JF,, Raoult D,, Fenollar F. 2013. Looking for Tropheryma whipplei source and reservoir in rural Senegal. Am J Trop Med Hyg 88:339343.
43. Müller SA,, Vogt P,, Altwegg M,, Seebach JD. 2005. Deadly carousel or difficult interpretation of new diagnostic tools for Whipple’s disease: case report and review of the literature. Infection 33:3942.
44. von Herbay A. 2001. Whipple’s disease. Histologic diagnosis after the discovery of Tropheryma whippelii. Pathologe 22:8288.
45. Raoult D,, Lepidi H,, Harle JR. 2001. Tropheryma whipplei circulating in blood monocytes. N Engl J Med 345:548.
46. Lepidi H,, Fenollar F,, Gerolami R,, Mege JL,, Bonzi MF,, Chappuis M,, Sahel J,, Raoult D. 2003. Whipple’s disease: immunospecific and quantitative immunohistochemical study of intestinal biopsy specimens. Hum Pathol 34:589596.
47. Fredricks DN,, Relman DA. 2001. Localization of Tropheryma whippelii rRNA in tissues from patients with Whipple’s disease. J Infect Dis 183:12291237.
48. Mallmann C,, Siemoneit S,, Schmiedel D,, Petrich A,, Gescher DM,, Halle E,, Musci M,, Hetzer R,, Göbel UB,, Moter A. 2010. Fluorescence in situ hybridization to improve the diagnosis of endocarditis: a pilot study. Clin Microbiol Infect 16:767773.
49. Hinrikson HP,, Dutly F,, Altwegg M. 2000. Evaluation of a specific nested PCR targeting domain III of the 23S rRNA gene of “Tropheryma whippelii” and proposal of a classification system for its molecular variants. J Clin Microbiol 38:595599.
50. Relman DA,, Lepp PW,, Sadler KN,, Schmidt TM. 1992. Phylogenetic relationships among the agent of bacillary angiomatosis, Bartonella bacilliformis, and other alpha-proteobacteria. Mol Microbiol 6:18011807.
51. Moter A,, Schmiedel D,, Petrich A,, Wiessner A,, Kikhney J,, Schneider T,, Moos V,, Göbel UB,, Reischl U. 2013. Validation of an rpoB gene PCR assay for detection of Tropheryma whipplei: 10 years’ experience in a national reference laboratory. J Clin Microbiol 51:38583861.
52. Marth T,, Fredericks D,, Strober W,, Relman DA. 1996. Limited role for PCR-based diagnosis of Whipple’s disease from peripheral blood mononuclear cells. Lancet 348:6667.
53. Geißdörfer W,, Wittmann I,, Röllinghoff M,, Schoerner C,, Bogdan C. 2001. Detection of a new 16S-23S rRNA spacer sequence variant (type 7) of Tropheryma whippelii in a patient with prosthetic aortic valve endocarditis. Eur J Clin Microbiol Infect Dis 20:762763.
54. Li W,, Fenollar F,, Rolain JM,, Fournier PE,, Feurle GE,, Müller C,, Moos V,, Marth T,, Altwegg M,, Calligaris-Maibach RC,, Schneider T,, Biagi F,, La Scola B,, Raoult D. 2008. Genotyping reveals a wide heterogeneity of Tropheryma whipplei. Microbiology 154:521527.
55. Wetzstein N,, Fenollar F,, Buffet S,, Moos V,, Schneider T,, Raoult D. 2013. Tropheryma whipplei genotypes 1 and 3, Central Europe. Emerg Infect Dis 19:341342.
56. Kowalczewska M,, Villard C,, Lafitte D,, Fenollar F,, Raoult D. 2009. Global proteomic pattern of Tropheryma whipplei: a Whipple’s disease bacterium. Proteomics 9:15931616.
57. Liang Z,, La Scola B,, Raoult D. 2002. Monoclonal antibodies to immunodominant epitope of Tropheryma whipplei. Clin Diagn Lab Immunol 9:156159.
58. Morgenegg S,, Maibach R,, Chaperon DN,, Herzog K,, Altwegg M. 2001. Antibodies against recombinant heat shock protein 65 of Tropheryma whipplei in patients with and without Whipple’s disease. J Microbiol Methods 47:299306.
59. Boulos A,, Rolain JM,, Mallet MN,, Raoult D. 2005. Molecular evaluation of antibiotic susceptibility of Tropheryma whipplei in axenic medium. J Antimicrob Chemother 55:178181.
60. Masselot F,, Boulos A,, Maurin M,, Rolain JM,, Raoult D. 2003. Molecular evaluation of antibiotic susceptibility: Tropheryma whipplei paradigm. Antimicrob Agents Chemother 47:16581664.
61. Cannon WR. 2003. Whipple’s disease, genomics, and drug therapy. Lancet 361:1916.
62. Fenollar F,, Perreal C,, Raoult D. 2014. Tropheryma whipplei natural resistance to trimethoprim and sulphonamides in vitro. Int J Antimicrob Agents 43:388390.
63. Keinath RD,, Merrell DE,, Vlietstra R,, Dobbins WOIII. 1985. Antibiotic treatment and relapse in Whipple’s disease. Long-term follow-up of 88 patients. Gastroenterology 88:18671873.
64. Feurle GE,, Junga NS,, Marth T. 2010. Efficacy of ceftriaxone or meropenem as initial therapies in Whipple’s disease. Gastroenterology 138:478486.
65. Lagier JC,, Fenollar F,, Lepidi H,, Giorgi R,, Million M,, Raoult D. 2014. Treatment of classic Whipple’s disease: from in vitro results to clinical outcome. J Antimicrob Chemother 69:219227.
66. Lagier JC,, Fenollar F,, Lepidi H,, Raoult D. 2011. Evidence of lifetime susceptibility to Tropheryma whipplei in patients with Whipple’s disease. J Antimicrob Chemother 66:11881189.
67. Feurle GE,, Moos V,, Schinnerling K,, Geelhaar A,, Allers K,, Biagi F,, Blaker H,, Moter A,, Loddenkemper C,, Jansen A,, Schneider T. 2010. The immune reconstitution inflammatory syndrome in Whipple disease: a cohort study. Ann Intern Med 153:710717.
68. Schneider T,, Stallmach A,, von Herbay A,, Marth T,, Strober W,, Zeitz M. 1998. Treatment of refractory Whipple disease with interferon-gamma. Ann Intern Med 129:875877.


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Symptoms and signs of infections

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Recommended therapy for Whipple’s disease ( )


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