Platelet Parameters and (1, 3)-β-D-Glucan as a Diagnostic and Prognostic Marker of Invasive Fungal Disease in Preterm Infants

Abstract

The diagnosis of neonatal invasive fungal disease (IFD) is difficult and often delayed. The platelet parameters and (1, 3)-β-D-Glucan (BG) may be useful for diagnosing IFD, but their diagnostic performance are not well characterized in neonates. We studied 63 preterm infants with IFD, 160 preterm infants without sepsis (preterm control), and 41 preterm infants with bacterial sepsis. Platelet parameters at the first day of onset of IFD and at the fourteenth day after antifungal treatment were evaluated. Serum BG was measured. Platelet count (PC), plateletcrit (PCT), and platelet distribution width (PDW) values were significantly lower, and mean platelet volume (MPV) values significantly higher in the IFD versus preterm control infants. PC and PCT values were much lower in infants with IFD versus bacterial sepsis, and there were significant differences in BG value between the two groups. After 14 days of antifungal treatment, significant elevations in PC, PCT, PDW and reductions in MPV levels in IFD group were observed. Receiver operating characteristic (ROC) curves showed that PC and PCT were strong predictors of IFD. The PC and PCT cut-offs for predicting IFD were 119.5 (sensitivity 78%, specificity 95%) and 0.21 (sensitivity 83%, specificity 85%), respectively. There were significant differences in PC and PCT levels between deceased and survived patients. The PC and PCT cut-offs for predicting deceased IFD were 39 (sensitivity 62%, specificity 86%) and 0.04 (sensitivity 50%, specificity 95%), respectively. The sensitivity in diagnosing IFD by a BG cutoff of ≥10pg/ml was 68.3% and specificity was 75.6%. PC and PCT levels in the BG ≥400 pg/ml group were significantly lower compared to the BG<400 pg/ml group. Platelet parameters and BG could be useful biomarkers for the diagnosis and prognosis of neonatal IFD.

Redundant Trojan horse and endothelial-circulatory mechanisms for host-mediated spread ofCandida albicansyeast

“…Conservation of adhesion molecules, cell types and anatomy among all vertebrates suggests that both mechanisms are likely to also be important in mammalian infection [68–71]. Clinical observations are consistent with our findings that C. albicans moves in the blood both inside and outside of phagocytes [72–75]. From a therapeutic standpoint, our results suggest that prevention of C. albicans dissemination will require interventions that block both endothelial and phagocyte-driven movement of yeast.…”

Performance of 1,3‐β‐D‐glucan for diagnosing invasive fungal diseases in children

“…Children with IFD had high BDG values, as already observed in adults [9][10][11][22][23][24][25] and in small paediatric series or case reports, [26][27][28][29][30][31] using 80 pg/mL as cut off for a positive test. The value of BDG cut off is a not negligible question especially in paediatrics, since BDG plasmatic concentrations ≥80 pg/ml have been observed both in the absence of IFD, and in healthy children.…”

“…10 making process. [14][15][16]18,33 Indeed, BDG has been proposed as a useful test in neonates even if using different diagnostic kits, 13,23,24,26 and our data seems in some way to confirm these observations, even if the low number of neonates enrolled in our study and the very low number of IFDs included in the study in this patients' population (indeed one case only) could explain why Se does not decrease as the cut off value increases, and render these results less conclusive. However, it must be stressed that in very low (< 1500 g) or extremely low (<1000 g) birth weight neonates the amount of blood and the frequency of sampling needed to perform the BDG test could represent the limiting steps for a screening test.…”

Evolving Invasive Neonatal Systemic Candidiasis, a Review

“…LBW (<2500 g) and earlier gestational age (29)(30)(31)(32) weeks) are found to be commonly associated with invasive candidiasis in neonates. Other risk factors identified in clinical studies to be associated with invasive candidiasis are vaginal birth, central catheters, day of life (>7), use of broad-spectrum antibiotics in neonates, antenatal steroids, premature rupture of membranes, mechanical ventilation, necrotizing enterocolitis and parenteral nutrition (Table 1) [1,14,13,17].…”

“…[10,29] Very few studies have been conducted in neonates on usability of these biomarkers in diagnosis of invasive candidiasis (Table 2). Although these tests show encouraging results, cost and lack of substantial data in neonates prevent their use in standard practice presently.…”