Although observed in diseased tissue, some organisms are nonculturable yet associated with specific disease processes, making the development of “traditional” diagnostic assays difficult (e.g., serology or antigen detection). With the ability to detect and classify bacteria using molecular techniques such as PCR to amplify ribosomal DNA sequences followed by sequencing and phylogenetic analysis, Tropheryma whipplei was identified as the causative agent of Whipple’s disease.

GENERAL CHARACTERISTICS

 Phylogenetic analysis shows that this organism is a gram positive actinomycete not closely related to any other genus known to cause infection.

EPIDEMIOLOGY, PATHOGENESIS, AND SPECTRUM OF DISEASE

 Whipple’s disease, found primarily in middle-aged men, is characterized by the presence of periodic acid-Schiff (PAS)–staining macrophages (indicating mucopolysaccharide or glycoprotein) in almost every organ system. The bacillus is observed in macrophages and affected tissues, but it has never been cultured. Patients develop diarrhea, weight loss, arthralgia, lymphadenopathy, hyperpigmentation, often a long history of joint pain, and a distended and tender abdomen. Neurologic and sensory changes often occur. Although less common than intestinal or articular involvement, cardiac manifestations can also occur, including endocarditis. It has been suggested that a cellular immune defect is involved in the pathogenesis of this disease.

LABORATORY DIAGNOSIS

 Detection of T. whipplei is limited to only a few laboratories using conventional and real-time PCR.

ANTIBIOTIC SUSCEPTIBILITY TESTING AND THERAPY

The organism is nonculturable, resulting in the inability to perform susceptibility testing. Patients usually respond well to long-term therapy with antibacterial agents, including trimethoprim/sulfamethoxazole, macrolides, aminoglycosides, tetracycline, and penicillin; tetracycline has been associated with serious relapses, however. Colchicine therapy appears to control symptoms. Without treatment the disease is uniformly fatal.

 PREVENTION

 Little is known about the prevention of this disease.

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