A point-of-need platform for rapid measurement of a host-protein score that differentiates bacterial from viral infection: Analytical evaluation

Hainrichson, Mary; Avni, Noa; Eden, Eran; Feigin, Paul D.; Gelman, Amir; Halabi, Salim; Hartog, Efrat; Hultén, Kristina G.; Ashkar, Jalal; Kalfon, Roy; Lamberth, Linda B.; Lewis, Shawna; Navon, Roy; Oved, Kfir; Raz-Pasteur, Ayelet; Senderovich, Naftalie; Shaham, Oded; Shraga, Meytal; Simon, Einav; Sommer, Lauren M; Zarchin, Oren; Carroll, Karen C.; Gottlieb, Tanya M.

doi:10.1016/j.clinbiochem.2022.04.012

Cited by 18 publications

(14 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High sensitivity was an advantage of IP-10 and IFN-γ analytical results in this technique, with LODs reaching ag/mL levels, comparable to other methods for IFN-γ and IP-10 (Tables S5 and S6). − ,,,− This strategy relied on our development of an enzyme-free associated expansion system based on the high affinity of aptamers, the CHA reaction, and the application of ion-selective identification nanomaterials and was unquestionably superior to the complicated amplification system-assisted approach, which, for the first time, accomplishes simple simultaneous homogeneous operation without the requirement for enzyme participation or wash-separation steps compared to the earlier IFN-γ and IP-10 approaches.…”

Section: Resultsmentioning

confidence: 99%

“…Several immune-based approaches, including colorimetric, electrochemical, chemiluminescence (CL), electrochemiluminescence, fluorescence, and filter paper methods, have been reported to detect IP-10 and IFN-γ in recent years. − The enzyme-linked immunosorbent assay (ELISA) and CL assay are now the most commonly used techniques in clinical practice for measuring IP-10 and IFN-γ (Scheme B). These methods employ solid-phase carriers or magnetic beads to coat the antigens or antibodies.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Nucleic Acid and Nanomaterial Synergistic Amplification Enables Dual Targets of Ultrasensitive Fluorescence Quantification to Improve the Efficacy of Clinical Tuberculosis Diagnosis

Shi,

Jiang,

Peng

et al. 2024

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

Interferon-γ (IFN-γ) release assays (IGRAs) are constrained by the limited diagnostic performance of a single indicator and the excessive Mycobacterium tuberculosis (Mtb) antigen stimulation time. This study presents a simultaneous, homogeneous, rapid, and ultrasensitive fluorescence quantification strategy for IFN-γ and IFN-γ-induced protein 10 (IP-10). This method relies on the high-affinity binding of aptamers to IFN-γ and IP-10, the enzyme-free catalytic hairpin assembly reaction, and the heightened sensitivity of CdTe quantum dots to Ag + and hairpin structure C-Ag + -C and carbon dots to Hg 2+ and hairpin structure T-Hg 2+ -T. Under optimized conditions, the selectivity of IFN-γ and IP-10 was excellent, with a linear range spanning from 1 to 100 ag/mL and low limits of detection of 0.3 and 0.5 ag/mL, respectively. Clinical practicality was confirmed through testing of 57 clinical samples. The dual-indicator combination detection showed 92.8% specificity and 93.1% sensitivity, with an area under the curve of 0.899, representing an improvement over the singleindicator approach. The Mtb antigen stimulation time was reduced to 8 h for 6/7 clinical samples. These findings underscore the potential of our approach to enhance the efficiency and performance of a tuberculosis (TB) clinical diagnosis.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nucleic Acid and Nanomaterial Synergistic Amplification Enables Dual Targets of Ultrasensitive Fluorescence Quantification to Improve the Efficacy of Clinical Tuberculosis Diagnosis

Shi,

Jiang,

Peng

et al. 2024

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

show abstract

“…Notably, BV's impact on antibiotic prescription in the ED requires availability of the BV result within the patient's visit, which is now possible as there is a rapid sample-to-result platform. Comparability of BV results produced by the ELISA platform (employed in the studies described here) and the rapid platform has been established for serum samples ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

BV score differentiates viral from bacterial-viral co-infection in adenovirus PCR positive children

et al. 2022

View full text Add to dashboard Cite

Background and objectivesAdenovirus causes acute respiratory illness that can mimic bacterial infection, making it challenging to differentiate adenoviral infection from adenoviral-bacterial co-infection. A host-protein score (BV score) for differentiating bacterial from viral infection that combines the expression levels of TNF-related apoptosis-induced ligand, interferon gamma-induced protein-10, and C-reactive protein exhibited a negative predictive value (NPV) of 98% in prior studies. Here we evaluate BV score's diagnostic accuracy in pediatrics with adenovirus PCR detection.MethodsThis is a sub-analysis of children aged 3 months to 20 years with adenovirus PCR-positive infection recruited prospectively in two previous cohort studies. Reference standard diagnosis (bacterial, viral or indeterminate) was based on expert adjudication. BV score ranges from 0 to 100 and provides three results based on predefined cutoffs: viral or other non-bacterial etiology (0 ≤ score < 35), equivocal (35 ≤ score ≤ 65), and bacterial or co-infection (65 < score ≤ 100). Experts were blinded to BV results.ResultsOut of 1,779 children, 142 had an adenovirus PCR-positive nasopharyngeal swab. Median age was 1.2 years (interquartile range 0.6–1.8), 50.7% were male and 52.8% were hospitalized. 12 cases were reference standard bacterial, 115 reference standard viral and 15 were indeterminate. BV score attained sensitivity of 100.0% (no false negatives), specificity of 89.5% (95% confidence interval: 83.2–95.8), and NPV of 100.0% (92.6–100.0). Equivocal rate was 19.7%.ConclusionsBV score accurately differentiated between adenoviral and bacterial-adenoviral co-infection in this cohort of children with PCR-positive adenovirus detection. This performance supports a potential to improve appropriate antibiotic use.

show abstract

“…Of note, ImmunoXpert™ is no longer available; (the BV score can be measured within 15 minutes from serum using a point-of-need immunoassay platform called MeMed Key® and the MeMed BV® test cartridge (MeMed, Israel; CE-IVD and FDA cleared)). The scores generated by ImmunoXpert and running MeMed BV on MeMed Key have been established as comparable [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

Bacterial vs viral etiology of fever: A prospective study of a host score for supporting etiologic accuracy of emergency department physicians

et al. 2023

View full text Add to dashboard Cite

Background A host-protein score (BV score) that combines the circulating levels of TNF-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein 10 (IP-10) and C-reactive protein (CRP) was developed for distinguishing bacterial from viral infection. This study assessed the potential of the BV score to impact decision making and antibiotic stewardship at the emergency department (ED), by comparing BV score’s performance to physician’s etiological suspicion at patient presentation. Methods Rosetta study participants, aged 3 months to 18 years with febrile respiratory tract infection or fever without source, were prospectively recruited in a tertiary care pediatric ED. 465 patients were recruited, 298 met eligibility criteria and 287 were enrolled. ED physician’s etiological suspicion was recorded in a questionnaire. BV score was measured retrospectively with results interpreted as viral, bacterial or equivocal and compared to reference standard etiology, which was adjudicated by three independent experts based on all available data. Experts were blinded to BV scores. Results Median age was 1.3 years (interquartile range 1.7), 39.7% females. 196 cases were reference standard viral and 18 cases were reference standard bacterial. BV score attained sensitivity of 88.9% (95% confidence interval: 74.4–100), specificity 92.1% (88.1–96.0), positive predictive value 53.3% (35.5–71.2) and negative predictive value 98.8% (97.1–100). Positive likelihood ratio was 11.18 (6.59–18.97) and negative likelihood ratio was 0.12 (0.03–0.45). The rate of BV equivocal scores was 9.4%. Comparing physician’s suspicion to BV score and to the reference standard, and assuming full adoption, BV score could potentially correct the physician’s diagnosis and reduce error ~2-fold, from 15.9% to 8.2%. Conclusions BV score has potential to aid the diagnostic process. Future studies are warranted to assess the impact of real-time BV results on ED practice.

show abstract

A point-of-need platform for rapid measurement of a host-protein score that differentiates bacterial from viral infection: Analytical evaluation

Cited by 18 publications

References 18 publications

Nucleic Acid and Nanomaterial Synergistic Amplification Enables Dual Targets of Ultrasensitive Fluorescence Quantification to Improve the Efficacy of Clinical Tuberculosis Diagnosis

Nucleic Acid and Nanomaterial Synergistic Amplification Enables Dual Targets of Ultrasensitive Fluorescence Quantification to Improve the Efficacy of Clinical Tuberculosis Diagnosis

BV score differentiates viral from bacterial-viral co-infection in adenovirus PCR positive children

Bacterial vs viral etiology of fever: A prospective study of a host score for supporting etiologic accuracy of emergency department physicians

Contact Info

Product

Resources

About