Clinical and microbiological characteristics of patients with Tropheryma whipplei detected in bronchoalveolar lavage fluid by metagenomic next-generation sequencing: a retrospective cohort study

Tropheryma whipplei (TW), the pathogen of Whipple’s disease, has recently been identified as potentially pathogenic in respiratory infections through metagenomic next-generation sequencing (mNGS) technology. However, its clinical significance in lung infections is still unclear due to its frequent co-detection with other pathogens and the lack of diagnostic standards. We retrospectively analyzed 74 patients with TW-positive bronchoalveolar lavage fluid (BALF) detected by mNGS from January 2018 to December 2022. Over the study period, a total of 1,543 BALF samples were subjected to mNGS analysis, resulting in a detection rate of 4.79% for TW. Clinical manifestations, imaging features, and microbiological data (including TW sequence quantification and co-pathogen profiles) were systematically evaluated. Radiographic outcomes were assessed via follow-up CT in 41 patients. The cohort (mean age 55 years, 52.7% male) predominantly presented with cough (71.6%), expectoration (59.5%), and dyspnea (31.1%). Characteristic CT findings included patchy opacities (74.3%) and multiple nodules (71.6%). Laboratory abnormalities included low hemoglobin (43/73, 58.9%), low albumin (38/64, 59.4%), and elevated inflammatory markers (CRP 53.2%, ESR 62.5%). TW was the sole pathogen in only 23.0% of cases, with common bacterial (64.9%) and fungal (25.7%) co-detection. Notably, TW log₁₀ reads were lower in patients with co-detection of Streptococcus pneumoniae or Pseudomonas aeruginosa (median [IQR]: 0.81 [0.43–2.54] vs. 2.57 [1.22–3.45] log₁₀ reads; P = 0.038), and higher in patients with low hemoglobin (median [IQR]: 2.73 [1.08–3.65] vs. 1.73 [0.30–2.70] log₁₀ reads; P = 0.045). In a limited retrospective comparison, anti-TW therapy was not associated with significant radiographic improvement in this cohort ( P = 0.295). In this descriptive and exploratory cohort, TW was frequently co-detected with other potential respiratory pathogens, making it difficult to attribute the clinical presentation to TW alone. TW log₁₀ reads were lower in patients with co-detection of S. pneumoniae or P. aeruginosa , and higher in patients with low hemoglobin. In a limited retrospective comparison, anti-TW therapy was not associated with significant radiographic improvement. These findings are descriptive and hypothesis-generating and highlight the need for prospective studies with standardized diagnostic and treatment protocols to clarify the clinical significance of TW detection in BALF. Not applicable.