Tropheryma whipplei native valve endocarditis diagnosed by sequencing of microbial cell-free DNA in plasma

Endocarditis is an important manifestation of extra-intestinal Whipple's disease. The etiologic agent, the bacterium Tropheryma whipplei, cannot be cultivated in clinical laboratories, making the diagnosis of this culture-negative infection challenging. Molecular methods have emerged as useful adjuncts for the diagnosis of culture-negative endocarditis.

A 67-year-old male was seen in an infectious disease clinic for evaluation of a possible infectious etiology of chronic musculoskeletal pain with exercise intolerance. He had a history of an embolic stroke 2 years earlier, echocardiographic evidence of aortic valve thickening, and multiple negative blood cultures. Following an evaluation that included serology and extended incubation blood culture, plasma was sent for metagenomic sequencing of microbial cell-free DNA, which was positive for Tropheryma whipplei.

The patient's musculoskeletal complaints and his exercise intolerance resolved after treatment with ceftriaxone and trimethoprim-sulfamethoxazole. To our knowledge, this is the first report of T. whipplei native valve endocarditis diagnosed by metagenomic sequencing.