Tropheryma whipplei in Pulmonary Infections: Microbial Competition with Streptococcus pneumoniae and Pseudomonas aeruginosa, Association with Anemia, and Lack of Benefit from Targeted Therapy - A Retrospective Cohort Study

Objective 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. Methods 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. Treatment efficacy was assessed via follow-up CT in 41 patients. Results The cohort (mean age 55 years, 47.3% 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 anemia (58.1%), hypoalbuminemia (51.4%), 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-infections. Notably, TW sequence counts were significantly lower when co-infected with Streptococcus pneumoniae or Pseudomonas aeruginosa (P = 0.038) and were significantly higher in anemic patients (P = 0.045). Targeted anti-TW therapy did not significantly improve radiographic outcomes in this cohort (P = 0.295). Conclusion This study suggests that respiratory TW often represents co-infection rather than primary pathogenicity. The bacterium exhibits complex ecological interactions within the lung microbiota and is associated with specific hematological abnormalities. These findings challenge the necessity of routine TW-targeted therapy in mixed infections and emphasize the need for diagnostic procedures integrating sequence quantification and clinical parameters.