Objective: Determining infection etiology can be difficult because viral and bacterial diseases often manifest similarly. A host protein test that computationally integrates the circulating levels of TNF-related apoptosis-induced ligand, interferon γ-induced protein-10, and C-reactive protein to differentiate between bacterial and viral infection (called MMBV) demonstrated high performance in multiple prospective clinical validation studies. Here, MMBV's diagnostic accuracy is evaluated in febrile children for whom physicians were uncertain about etiology when applied at the physician's discretion.
Methods: Patients aged 3 months to 18 years were retrospectively recruited (NCT03075111; SPIRIT study; 2014-2017). Emergency department physician's etiological suspicion and certainty level were recorded in a questionnaire at blood-draw. MMBV results are based on predefined score thresholds: viral/non-bacterial etiology (0 ≤ score <35), equivocal (35 ≤ score ≤65), and bacterial or coinfection (65 < score ≤100). Reference standard etiology (bacterial/viral/indeterminate) was adjudicated by 3 independent experts based on all available patient data. Experts were blinded to MMBV. MMBV and physician's etiological suspicion were assessed against the reference standard.
Results: Of 3003 potentially eligible patients, the physicians were uncertain about infection etiology for 736 of the cases assigned a reference standard (128 bacterial, 608 viral). MMBV performed with sensitivity 89.7% (96/107; 95% confidence interval 82.4-94.3) and specificity 92.6% (498/538; 95% confidence interval 90.0-94.5), significantly outperforming physician's etiological suspicion (sensitivity 49/74 = 66.2%, specificity 265/368 = 72.0%; P < .0001). MMBV equivocal rate was 12.4% (91/736).
Conclusions: MMBV was more accurate in determining etiology compared with physician's suspicion and had high sensitivity and specificity according to the reference standard.