SynthesisFrontiers in cellular and infection microbiology2026
A meta-analysis-informed diagnostic stratification tool for invasive pulmonary aspergillosis in severe fever with thrombocytopenia syndrome: systematic review, meta-analysis, and single-center cohort-based assessment.
Synthesis in Frontiers in cellular and infection microbiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: This study aimed to develop and assess a meta-analysis-informed diagnostic stratification tool for invasive pulmonary aspergillosis (IPA) in patients with severe fever with thrombocytopenia syndrome (SFTS). Methods: A systematic review and meta-analysis were conducted to identify bedside clinical factors associated with IPA/SFTS-associated pulmonary aspergillosis (SAPA) in patients with SFTS. Because individual participant data were unavailable, pooled study-level odds ratios were translated into a pragmatic three-variable diagnostic stratification score rather than a conventional individual-level prediction model. The tool was assessed in a separate single-center retrospective cohort of 220 patients with SFTS, among whom 63 (28.6%) met the clinically ascertained IPA/SAPA endpoint. Results: Six studies involving 2,342 patients with SFTS, including 407 patients with IPA/SAPA, were included in the quantitative meta-analysis. In the primary random-effects analyses, neurological symptoms showed the clearest pooled association with increased IPA/SAPA risk, whereas ICU admission and corticosteroid use showed positive but less precise pooled directions of effect. The final three-variable score assigned 9 points for neurological symptoms, 9 points for ICU admission, and 6 points for corticosteroid use, yielding a total score range of 0-24 points. In the single-center cohort-based assessment, the diagnostic stratification tool showed encouraging discrimination, with an AUC of 0.910 (95% CI, 0.869-0.951) and a Brier score of 0.097 after cohort-based logistic recalibration. The observed IPA/SAPA incidence increased stepwise across low-, medium-, and high-risk groups: 3.7% (4/108), 22.8% (13/57), and 83.6% (46/55), respectively. Conclusion: This meta-analysis-informed diagnostic stratification tool showed encouraging cohort-based risk separation in a single-center retrospective assessment. It may help prioritize fungal diagnostic work-up and surveillance intensity in patients with SFTS and support more targeted diagnostic resource allocation and antifungal stewardship. However, it should not be used as a stand-alone basis for antifungal treatment decisions or as a broadly generalizable individual-level prediction model. External validation, local recalibration, and prospective multicenter evaluation are required before clinical implementation. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=5115813, identifier CRD420251115813.
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