Predictors of Candidemia during Febrile Episode in Lymphoreticular Malignancy Affecting Paediatric Population

Abstract

Limited studies on candidemia in malignancy in the paediatric population from developing countries show a high incidence, high morbidity and a unique epidemiology as compared to developed nations. Our prospective observational study aimed to explore the prevalence of invasive candidiasis, especially candidemia, in febrile paediatric patients with lymphoreticular malignancy. A sample size of 49 children, with 100 recorded febrile episodes was studied. The relevance of candida colonization and mannan antigen detection as indicators of impending candidemia was evaluated. Genotypic identification of the yeast isolates was followed by sequence analysis using the NCBI-BLAST program, and the generation of the phylogenetic tree using MEGA 6.0 software. We observed a 5% prevalence of candidemia among febrile paediatric patients with lymphoreticular malignancy, predominantly caused by non-albicans candida. Colonization at multiple anatomical sites decreased from day 1 to day 8 of febrile episodes. Significant candida colonization (colonization index ≥0.5) was seen in a larger proportion of candidemia patients on day 1 and day 4 (p < 0.001) displaying a definite association between the two. The receiver operator characteristic (ROC) curve analysis for mannan antigen level revealed a cut-off of ≥104.667 pg/mL, suitable for predicting candidemia with a sensitivity of 100%, specificity of 92% and area under ROC value of 0.958 (95% CI: 0.915–1; p < 0.001). A phylogenetic tree with three population groups, clade 1, 2 and 3, consisting of Candida auris (1), Candida tropicalis (2) and Candida parapsilosis (2), respectively, was generated. The diagnosis of candidemia based on mannan antigen detection gives early results and has high negative predictive values. It can be combined with other biomarkers to increase sensitivity, specificity and positive predictive value.