In 1907, the US-American pathologist George Hoyt Whipple (Biography) reported “a hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues”. ( 1 )  He interpreted his autopsy findings as intestinal lipodystrophy.

In 1949, a newly developed histochemical stain was first applied to tissue from a patient with the disease. The positive reaction with Periodic Acid Schiff´s reagent (PAS) revealed that the foamy macrophages, which were described previously by Whipple, did in fact contain a glycoprotein material but not lipids. ( 2 )

In 1960/1961, when electron microscopy entered into medicine, the PAS positive material in the cytoplasm of macrophages was identified as rod-shaped bacteria. ( 3, 4 , 5 ) Since, Whipple´s disease is considered to be an infective disorder which can be treated successfully with antibiotics.

In 1963 and 1970, autopsy findings (in untreated patients) and clinical observations (in untreated or treated patients) illustrated that infection with the gram-positive Whipple´s disease bacterium is frequently not limited to the small intestine and its lymph nodes, and may also affect any other organs. ( 6, 7 )  Thus, Whipple´s disease is a systemic disorder.

In 1991 and 1992, with the advent of molecular methods, the then still uncultured bacterium of Whipple´s disease was eventually characterized as a new and peculiar species within the bacterial family of actinomycetes. ( 8, 9 )  A new name was proposed, Tropheryma whippelii. ( 9 ) T his name is widely used, but was modified by some to Tropheryma whipplei.  

in 2000, the first successful in-vitro cultivation was done supported by human fibroblasts. (10)

Since 2003, the complete bacterial genome is sequenced and analyzed. ( 11, 12 ) 


  1. Whipple GH (1907). A hitherto undescribed disease characterized anatomically by deposits of fat and fatty acids in the intestinal and mesenteric lymphatic tissues. Johns Hopkins Hosp Bull 18: 382-391
  2. Black-Schaffer B (1949). The tinctorial demonstration of a glycoprotein in Whipple´s disease.  Proc Soc Exp Biol Med 72: 225-227
  3. Cohen AS, Schimmel EM, Holt PR, Isselbacher KJ (1960). Ultrastructural abnormalities in Whipple´s disease. Proc Soc Exp Biol Med 105: 411-414
  4. Chears WC, Ashworth (1961). Electron microscopic study of the intestinal mucosa in Whipple´s disease. Demonstration of encapsulated bacilliform bodies in the lesion. Gastroenterology 41:129-138
  5. Yardley JH, Hendrix TR (1961). Combined electron and light microscopy on Whipple´s disease. Demonstration of “bacillary bodies” in the intestine. Bull Johns Hopkins Hosp 109: 80-98
  6. Enzinger FM, Helwig EB (1963). Whipple´s disease. A review of the literature and report of 15 patients. Virchows Archiv 336: 238-269
  7. Maizel H, Ruffin JM, Dobbins WO III (1970). Whipple´s disease: a review of 19 patients from one hospital and review of the literature since 1950. Medicine 49: 175-205
  8. Wilson KH, Blitchington R, Frothingham R, Wilson JAP (1991). Phylogeny of the Whipple´s disease-associated bacterium. Lancet 338: 474-475
  9. Relman DA, Schmidt TM, MacDermott RP, Falkow S (1992). Identification of the uncultured bacillus of Whipple´s disease. N Engl J Med 327: 293-301
  10. Raoult D, Birg ML, La Scola B, Fournier PE, Enea M, Lepidi H, Roux V, Piette JC, Vandenesch F, Vital-Durand D, Marrie TJ (2000)
    Cultivation of the bacillus of Whipple´s disease. N Engl J Med 342: 620-625
  11. Bentley S, Maiwald M, Murphy LD,  et al. (2003). Sequence and analysis of the genome of the Whipple´s disease bacterium Tropheryma whipplei. Lancet 361: 637-644
  12. Raoult D, Ogata H, Audic S, et al: (2003) Tropheryma whipplei twist: A human pathogenic actinobacteria with a reduced genome. Genome Res 13:1800-18nn
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