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Identification of early biomarkers in a rabbit model of primary Candida pneumonia
Gang Lu1, Chen Wang2, Chunrong Wu1
1Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, No. 128 Ruili Road, Shanghai, 200240, China.
Background:
Candida albicans is an opportunistic pathogen, but since it also belongs to the normal fungal flora, positive sputum culture as the solely basis for the diagnosis of invasive Candida albicans pneumonia can easily lead to excessive antifungal therapy. Therefore, identification of a pneumonia biomarker might improve diagnostic accuracy.
Methods:
A rabbit model was established by inoculating 5 × 107 cfu/mL C. albicans into the trachea of 20 rabbits with 20 rabbits as control group. Infection was monitored by chest thin-layer computed tomography (CT). 2 mL blood samples were collected daily during each infection and serum levels of potential biomarkers were measured by enzyme-linked immunosorbent assay (ELISA). Seven-day post-inoculation the rabbits were sacrificed by CO2 asphyxiation and lung tissue was histopathologically examined and blood was brought to culture. Data were statistically analyzed.
Results:
Infection became evident as early as day 3 post-inoculation. The levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), soluble hemoglobin-haptoglobin scavenger receptor (sCD163), procalcitonin (PCT) and tumor necrosis factor-α (TNF-α) were elevated in the experimental group compared to the control (P < 0.01), whereas the levels of C-reactive protein (CRP), interleukin-6 (IL-6), IL-8 and IL-10 showed no significant differences (P > 0.05). The dynamic curves of the levels of CRP, IL-6, IL-8, IL-10, SCD163 and TNF-α in both groups demonstrated a similar trend during infection but differences between the groups was observed only in the sTREM-1 levels. Receiver-operating characteristics (ROC) curve analysis showed that the sensitivity and specificity were 85 and 80% for sTREM-1 (cut-off value: 45.88 pg/mL) and 80 and 75% for SCD163 (cut-off value: 16.44 U/mL), respectively. The values of the area under the ROC curve (AUCROC) of sTREM-1 and SCD163 were 0.882 (95% CI: 0.922-0.976) and 0.814 (95% CI: 0.678-0.950), respectively. Other markers did not exhibit significant differences.
Conclusion:
sTREM-1 and SCD163 might be suitable biomarkers for pneumonia.
Insights
Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and soluble hemoglobin-haptoglobin scavenger receptor (sCD163) show promise as biomarkers for diagnosing invasive Candida albicans pneumonia. These markers may help improve diagnostic accuracy and reduce unnecessary antifungal treatments.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Candida albicans is an opportunistic pathogen and part of normal fungal flora.
- Positive sputum cultures alone can lead to over-treatment of invasive Candida albicans pneumonia.
- Biomarker identification is crucial for improving diagnostic accuracy.
Purpose of the Study:
- To evaluate potential biomarkers for diagnosing invasive Candida albicans pneumonia.
- To assess the diagnostic utility of sTREM-1 and sCD163 in a rabbit model of pneumonia.
Main Methods:
- A rabbit model of Candida albicans pneumonia was established.
- Serum biomarker levels (sTREM-1, sCD163, PCT, TNF-α, CRP, IL-6, IL-8, IL-10) were measured using ELISA.
- Chest CT scans, histopathology, and blood cultures were used for monitoring and diagnosis.
Main Results:
- sTREM-1 and sCD163 levels were significantly elevated in infected rabbits compared to controls.
- sTREM-1 demonstrated 85% sensitivity and 80% specificity (AUC 0.882).
- sCD163 showed 80% sensitivity and 75% specificity (AUC 0.814).
Conclusions:
- sTREM-1 and sCD163 are potential biomarkers for invasive Candida albicans pneumonia.
- These biomarkers may aid in differentiating true infections from colonization.
- Further validation in clinical settings is warranted.
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