Correspondence

Culture of T. whipplei from the Stool of a Patient with Whipple's Disease

N Engl J Med 2006; 355:1503-1505October 5, 2006

Article

To the Editor:

Tropheryma whipplei (formerly T. whippelii) causes Whipple's disease, an infectious disorder involving the digestive tract.1 The organism can be seen within macrophages in the duodenum, but T. whipplei was first isolated from specimens of human mitral valve.1 Molecular analysis of stool samples with the use of the polymerase chain reaction (PCR) has shown DNA of T. whipplei in patients with Whipple's disease. The DNA of the organism has also been found in unaffected people2 and in wastewater samples.2,3

T. whipplei has not been cultured from stool samples because of the large number of contaminating bacteria. While investigating the possibility of the transmission of Whipple's disease during endoscopy, we found that T. whipplei was resistant to decontamination with glutaraldehyde.4

We report the culture of T. whipplei from experimentally and naturally infected stool samples in a specific axenic medium5 after a decontamination procedure (Figure 1Figure 1Culture of Tropheryma whipplei from a Stool Sample from the Patient and from Experimentally Infected Stool Samples (Samples A, B, and C) in a Specific Axenic Medium (SAM) and the Effect of Gluteraldehyde on T. whipplei.).4 Infected stool was obtained from a 36-year-old woman who first received a diagnosis of Whipple's disease in March 1995; she had PCR-positive stools during relapses in 2000 and 2004. Glutaraldehyde slowed the growth of T. whipplei (Figure 1) in our control cultures, and growth of T. whipplei was observed in experimentally infected stools after 7 months. The number of copies of DNA in the culture of stool from the patient did not increase after 7 months, so we centrifuged the medium and reinoculated the pellet into fresh specific axenic medium 8 and 9 months after inoculation. At months 10 and 11, the growth of T. whipplei, evaluated by PCR and immunofluorescence, became exponential.5 The strain we isolated from the patient is now established and has been subcultured three times. We used genotyping to confirm that the isolated strain was that found in the duodenal-biopsy specimen from the patient and that no other bacteria were associated with the sample (see supplementary data 1 in the Supplementary Appendix, available with the full text of this letter at www.nejm.org).

Although T. whipplei DNA has previously been found in feces, we found viable bacteria in feces, and we speculate that Whipple's disease may be linked to fecal–oral contamination. Our study also confirms that T. whipplei is resistant to glutaraldehyde, a unique feature for a bacterium, since this product is widely used for disinfection.5 Our study has revealed a method of isolating strains of T. whipplei from patients, asymptomatic carriers, and the environment. Comparison of the genomic content of these strains could lead to the identification of pathogenic factors.

Didier Raoult, M.D., Ph.D.
Florence Fenollar, M.D., Ph.D.
Marie-Laure Birg
Université de la Méditerranée, 13385 Marseille CEDEX 5, France
didier.raoult@gmail.com

5 References

1. 1

   Raoult D, Birg ML, La Scola B, et al. Cultivation of the bacillus of Whipple's disease. N Engl J Med 2000;342:620-625[Erratum, N Engl J Med 2000;342:1538.]
   Full Text | Web of Science | Medline

2. 2

   Maibach RC, Dutly F, Altwegg M. Detection of Tropheryma whipplei DNA in feces by PCR using a target capture method. J Clin Microbiol 2002;40:2466-2471
   CrossRef | Web of Science | Medline

3. 3

   Maiwald M, Schuhmacher F, Ditton HJ, von Herbay A. Environmental occurrence of the Whipple's disease bacterium (Tropheryma whippelii). Appl Environ Microbiol 1998;64:760-762
   Web of Science | Medline

4. 4

   La Scola B, Rolain JM, Maurin M, Raoult D. Can Whipple's disease be transmitted by gastroscopes? Infect Control Hosp Epidemiol 2003;24:191-194
   CrossRef | Web of Science | Medline

5. 5

   Renesto P, Crapoulet N, Ogata H, et al. Genome-based design of a cell-free culture medium for Tropheryma whipplei. Lancet 2003;362:447-449
   CrossRef | Web of Science | Medline

Citing Articles (16)

Citing Articles

1. 1

   Florence Fenollar, Thierry Ponge, Bernard La Scola, Jean-Christophe Lagier, Maëva Lefebvre, Didier Raoult. (2011) First isolation of Tropheryma whipplei from bronchoalveolar fluid and clinical implications. Journal of Infection
   CrossRef

2. 2

   V. Moos, T. Schneider. (2011) Changing paradigms in Whipple’s disease and infection with Tropheryma whipplei. European Journal of Clinical Microbiology & Infectious Diseases 30:10, 1151-1158
   CrossRef

3. 3

   V. Moos, C. Loddenkemper, T. Schneider. (2011) Infektionen mit Tropheryma whipplei. Der Pathologe 32:5, 362-370
   CrossRef

4. 4

   Florence Fenollar, François Nicoli, Claire Paquet, Hubert Lepidi, Patrick Cozzone, Jean-Christophe Antoine, Jean Pouget, Didier Raoult. (2011) Progressive dementia associated with ataxia or obesity in patients with Tropheryma whipplei encephalitis. BMC Infectious Diseases 11:1, 171
   CrossRef

5. 5

   Benoit Desnues, Khatoun Al Moussawi, Florence Fenollar. (2010) New insights into Whipple’s disease and Tropheryma whipplei infections. Microbes and Infection 12:14-15, 1102-1110
   CrossRef

6. 6

   Emmanouil Angelakis, Florence Fenollar, Hubert Lepidi, Marie-Laure Birg, Didier Raoult. (2010) Tropheryma whipplei in the skin of patients with classic Whipple’s disease. Journal of Infection 61:3, 266-269
   CrossRef

7. 7

   Christos St. Basagiannis, George S. Panagoulias, Nicholas Tentolouris, Stavros Basoukeas, Dimitrios Sambaziotis, Spiros D. Ladas. (2010) Whipple Disease. Southern Medical Journal 103:4, 353-356
   CrossRef

8. 8

   Rish K. Pai, Rebecca Wilcox, John Hart. 2009. Molecular Gastrointestinal, Liver, and Pancreatic Pathology. , 269-295.
   CrossRef

9. 9

   Florence Fenollar, Sonia Laouira, Hubert Lepidi, Jean‐Marc Rolain, Didier Raoult. (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. Clinical Infectious Diseases 47:5, 659-667
   CrossRef

10. 10

    Nawal Bakkali, Florence Fenollar, Silpak Biswas, Jean‐Marc Rolain, Didier Raoult. (2008) Acquired Resistance to Trimethoprim‐Sulfamethoxazole during Whipple Disease and Expression of the Causative Target Gene. The Journal of Infectious Diseases 198:1, 101-108
    CrossRef

11. 11

    Florence Fenollar, Michèle Trani, Bernard Davoust, Bettina Salle, Marie‐Laure Birg, Jean‐Marc Rolain, Didier Raoult. (2008) Prevalence of Asymptomatic Tropheryma whipplei Carriage among Humans and Nonhuman Primates. The Journal of Infectious Diseases 197:6, 880-887
    CrossRef

12. 12

    Thomas Schneider, Verena Moos, Christoph Loddenkemper, Thomas Marth, Florence Fenollar, Didier Raoult. (2008) Whipple's disease: new aspects of pathogenesis and treatment. The Lancet Infectious Diseases 8:3, 179-190
    CrossRef

13. 13

    Klaus Mönkemüller, Lucia C. Fry, Ulrike von Arnim, Helmut Neumann, Matthias Evert, Peter Malfertheiner. (2008) Whipple’s Disease: An Endoscopic and Histologic Study. Digestion 77:3-4, 161-165
    CrossRef

14. 14

    Malgorzata Kowalczewska, Didier Raoult. (2007) Advances in Tropheryma whipplei research: the rush to find biomarkers for Whipple’s disease. Future Microbiology 2:6, 631-642
    CrossRef

15. 15

    Xavier Puéchal, Florence Fenollar, Didier Raoult. (2007) Cultivation ofTropheryma whipplei from the synovial fluid in Whipple's arthritis. Arthritis & Rheumatism 56:5, 1713-1718
    CrossRef

16. 16

    Fenollar, Florence, Puéchal, Xavier, Raoult, Didier, . (2007) Whipple's Disease. New England Journal of Medicine 356:1, 55-66
    Full Text