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Tropheryma whipplei

Whipple’s disease is caused by infection with Tropheryma whipplei, which is a ubiquitous environmental organism. The bacterium has been identified in fecal samples in up to 20% of asymptomatic persons, but clinical manifestations of infection occur in only 1 case per 1 million persons annually.  Infection most commonly occurs in males of European ancestry.

Infection commonly affects the duodenum causing weight loss, diarrhea, abdominal pain, arthralgia and lymphadenopathy. Many of these features develop over a period of 6 to 8 years before diagnosis. Less common findings include oculomasticatory myorhythmia, melanoderma in sun-exposed areas of the body, nonnecrotizing granulomas of the lymph nodes, and ascites. Up to 50% of patients have CNS disease. Common laboratory findings include hypoalbuminemia and anemia.

The diagnosis of Whipple’s disease is often delayed because of its rarity and many nonspecific symptoms and signs. Diagnostic tests for Whipple’s disease include histologic examination of tissue biopsies for periodic acid–Schiff (PAS)-positive granules within macrophages. Confirmation can be obtained withimmunohistochemical staining of macrophages with T. whipplei–specific antibody. A PCR assay for Tropheryma whipplei DNA can be performed on whole blood. Diagnosis of Whipple’s disease requires at least two of these three tests to be positive.

The disease is fatal if left untreated. Prolonged antibiotic regimens with blood–brain barrier penetration cure most patients. Standard therapy is a 14-day course of ceftriaxone followed by a 1-year course of trimethoprim–sulfamethoxazole.

Specimen requirement for PCR is a lavender top tube of blood. 


Odio CD, Cryptic Cachexia, N Engl J Med 2020; 383:68-74. DOI:10.1056/NEJMcps1817531

Sloan LM, Rosenblatt JE, Cockerill FR III: Detection of Tropheryma whipplei DNA in clinical specimens by LightCycler real-time PCR. J Clin Microobiol 2005;43:3516-3518

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