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Multicenter Prospective Study of Biomarkers for Diagnosis of Invasive Candidiasis in Children and Adolescents. Clin Infect Dis 2022 Aug 25;75(2):248-259

Date

02/09/2022

Pubmed ID

35134165

Pubmed Central ID

PMC9890499

DOI

10.1093/cid/ciab928

Scopus ID

2-s2.0-85132121704 (requires institutional sign-in at Scopus site)   6 Citations

Abstract

BACKGROUND: Diagnosis of invasive candidiasis (IC) relies on insensitive cultures; the relative utility of fungal biomarkers in children is unclear.

METHODS: This multinational observational cohort study enrolled patients aged >120 days and <18 years with concern for IC from 1 January 2015 to 26 September 2019 at 25 centers. Blood collected at onset of symptoms was tested using T2Candida, Fungitell (1→3)-β-D-glucan, Platelia Candida Antigen (Ag) Plus, and Platelia Candida Antibody (Ab) Plus assays. Operating characteristics were determined for each biomarker, and assays meeting a defined threshold considered in combination. Sterile site cultures were the reference standard.

RESULTS: Five hundred participants were enrolled at 22 centers in 3 countries, and IC was diagnosed in 13 (2.6%). Thirteen additional blood specimens were collected and successfully spiked with Candida species, to achieve a 5.0% event rate. Valid T2Candida, Fungitell, Platelia Candida Ag Plus, and Platelia Candida Ab Plus assay results were available for 438, 467, 473, and 473 specimens, respectively. Operating characteristics for T2Candida were most optimal for detecting IC due to any Candida species, with results as follows: sensitivity, 80.0% (95% confidence interval, 59.3%-93.2%), specificity 97.1% (95.0%-98.5%), positive predictive value, 62.5% (43.7%-78.9%), and negative predictive value, 98.8% (97.2%-99.6%). Only T2Candida and Platelia Candida Ag Plus assays met the threshold for combination testing. Positive result for either yielded the following results: sensitivity, 86.4% (95% confidence interval, 65.1%- 97.1%); specificity, 94.7% (92.0%-96.7%); positive predictive value, 47.5% (31.5%-63.9%); and negative predictive value, 99.2% (97.7%-99.8%).

CONCLUSIONS: T2Candida alone or in combination with Platelia Candida Ag Plus may be beneficial for rapid detection of Candida species in children with concern for IC.

CLINICAL TRIALS REGISTRATION: NCT02220790.

Author List

Fisher BT, Boge CLK, Xiao R, Shuster S, Chin-Quee D, Allen J, Shaheen S, Hayden R, Suganda S, Zaoutis TE, Chang YC, Yin DE, Huppler AR, Danziger-Isakov L, Muller WJ, Roilides E, Romero J, Sue PK, Berman D, Wattier RL, Halasa N, Pong A, Maron G, Soler-Palacin P, Hutto SC, Gonzalez BE, Salvatore CM, Rajan S, Green M, Doby Knackstedt E, Hauger SB, Steinbach WJ

Author

Anna H. Huppler MD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Antigens, Fungal
Biomarkers
Candida
Candidiasis
Candidiasis, Invasive
Child
Humans
Prospective Studies
Sensitivity and Specificity