Abstract
BACKGROUND: Distinguishing viral from bacterial infections in febrile children remains challenging despite available biomarkers. MMBV is a promising host-protein biosignature that computationally integrates TNF-related apoptosis-induced ligand, interferon-γ-induced protein-10, and C-reactive protein. MMBV uses predefined score thresholds for viral/non-bacterial (0–35), equivocal (36–65) and bacterial (66–100) etiologies. We conducted a systematic review and meta-analysis to evaluate MMBV diagnostic accuracy in febrile children. METHODS: Embase, MEDLINE, the Cochrane Library, Scopus, and CINAHL were searched until July 1, 2024. Studies evaluating MMBV diagnostic accuracy in febrile children, comparing the results of the MMBV score with a predefined reference standard established by an expert panel, were included. Two investigators independently screened, extracted data and evaluated the quality of eligible/included studies using the QUADAS-2 tool. Aggregate estimates of sensitivities and specificities were calculated with 95% confidence intervals (CI), overall and by type of infections. RESULTS: Of 486 studies identified, 14 met inclusion criteria, and nine were included in the meta-analysis. The pooled sensitivity and specificity estimates were 0.87 (95%CI 0.79–0.92, I(2) 55.6%) and 0.93 (95%CI 0.92–0.94, I(2) 0.0%), respectively. Pooled sensitivity and specificity for studies on febrile children, regardless of source, were 0.86 (95%CI 0.82–0.89, I(2) 0.0%) and 0.93 (95%CI 0.92–0.94, I(2) 0.0%). For studies on respiratory infections and fever without source, they were 0.89 (95%CI 0.79–0.95, I(2) 75.4%) and 0.93 (95%CI 0.91–0.94, I(2) 15.0%) CONCLUSIONS: MMBV showed high diagnostic accuracy, and results remained consistently elevated across sub-analyses. Additional studies are needed to evaluate its effectiveness in reducing unnecessary antibiotic prescriptions in febrile children. STUDY PROTOCOL REGISTRATION NUMBER: The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the number CRD42024506430. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=506430. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13052-025-02185-3.