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

**Authors:** Peter M. Rabinowitz, Ritika Walia, Paul Pottinger, Joshua A. Lieberman

PMC · DOI: 10.1128/asmcr.00070-25 · ASM Case Reports · 2025-10-01

## TL;DR

A new case of heart infection caused by Tropheryma whipplei was diagnosed using DNA sequencing of blood plasma, offering a novel diagnostic approach.

## Contribution

This is the first report of T. whipplei native valve endocarditis diagnosed using metagenomic sequencing of microbial cell-free DNA.

## Key findings

- Metagenomic sequencing of plasma detected T. whipplei in a patient with suspected endocarditis.
- The patient's symptoms resolved after treatment with ceftriaxone and trimethoprim-sulfamethoxazole.
- The diagnosis was confirmed without traditional culture methods, which typically fail for T. whipplei.

## Abstract

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.

## Linked entities

- **Chemicals:** ceftriaxone (PubChem CID 5479530), trimethoprim-sulfamethoxazole (PubChem CID 358641)
- **Diseases:** Whipple’s disease (MONDO:0005116), endocarditis (MONDO:0005025)
- **Species:** Tropheryma whipplei (taxon 2039)

## Full-text entities

- **Diseases:** infection (MESH:D007239), embolic stroke (MESH:D000083262), chronic musculoskeletal pain (MESH:D059352), Endocarditis (MESH:D004696), infectious disease (MESH:D003141), musculoskeletal (MESH:D009140), Whipple's disease (MESH:D008061)
- **Chemicals:** ceftriaxone (MESH:D002443), trimethoprim-sulfamethoxazole (MESH:D015662)
- **Species:** Tropheryma whipplei (species) [taxon 2039], Homo sapiens (human, species) [taxon 9606]

## Full text

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## References

17 references — full list in the complete paper: https://tomesphere.com/paper/PMC12584185/full.md

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Source: https://tomesphere.com/paper/PMC12584185