Application of Mass Spectrometry Technology to Early Diagnosis of Invasive Fungal Infections

J Clin Microbiol. 2016 Nov;54(11):2786-2797. doi: 10.1128/JCM.01655-16. Epub 2016 Sep 7.

Abstract

We recently developed a mass spectrometry (MS) procedure based on the detection of a serum disaccharide (MS-DS) in patients with invasive candidiasis (IC). Here, we compare the performance of MS-DS for the diagnosis of IC, invasive aspergillosis (IA), and mucormycosis (MM) with those of commercially available antigen detection tests. This retrospective study included 48 patients (23 IC patients [74 serum samples], 15 IA patients [40 serum samples], and 10 MM patients [15 serum samples]) and 49 appropriate controls (102 serum samples). MS-DS, mannan (Mnn), galactomannan (GM), and (1,3)-β-d-glucan (BDG) were detected by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) MS, Platelia, and Fungitell assays, respectively. For IC, the sensitivity and specificity of the MS-DS index, BDG detection, and Mnn detection were 62% and 84%, 82% and 60%, and 33% and 94% per serum sample and 83% and 69%, 96% and 31%, and 39% and 86% per patient, respectively. For IA, the corresponding values in comparison to BDG and GM detection were 83% and 81%, 62% and 95%, and 62% and 100% per serum sample and 93% and 76%, 87% and 90%, and 93% and 100% per patient, respectively. Nine of the 10 MM patients had a positive MS-DS result. MS-DS gave an early diagnosis in IC (73% positivity before blood culture), IA (positive before GM detection in six patients), and MM (positivity mainly preceded the date of diagnosis) patients. For IC, persisting MS-DS was associated with a poor prognosis. The different biomarkers were rarely detected simultaneously, suggesting different kinetics of release and clearance. For IA, MS-DS provided better complementation to GM monitoring than BDG monitoring. MS-DS detects panfungal molecules circulating during invasive fungal infections. The performance of MS-DS compared favorably with those of biological tests currently recommended for monitoring at-risk patients. Further validation of this test in multicenter studies is required.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Early Diagnosis*
  • Female
  • Humans
  • Invasive Fungal Infections / diagnosis*
  • Male
  • Microbiological Techniques / methods*
  • Middle Aged
  • Retrospective Studies
  • Sensitivity and Specificity
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*
  • Young Adult

Grants and funding

This work, including the efforts of Boualem Sendid, Nadine François, Julien Poissy, and Daniel Poulain, was funded by Programme Hospitalier de Recherche Clinique du Ministère des Affaires Sociales, de la Santé et de la Ville 1918, 2011.