title: Blood Aspergillus RNA is a promising alternative biomarker for invasive aspergillosis.
abstract: A critical challenge for the successful application of antifungal therapies for invasive aspergillosis (IA) is a lack of reliable biomarkers to assess early treatment response. Patients with proven or probable IA were prospectively enrolled, and serial blood samples were collected at 8 specified time points during 12-week antifungal therapy. Total nucleic acid was extracted from 2.5 ml blood and tested for Aspergillus-specific RNA by a pan-Aspergillus real-time nucleic acid sequence-based amplification (NASBA) assay. Serum 1, 3-β-D-glucan (BG) and galactomannan (GM) were measured in parallel. Clinical outcome was evaluated at 6 and 12 weeks. Overall, 48/328 (14.6%) blood samples from 29/46 (63%) patients had positive NASBA detection at baseline and/or some point during the study. Positive NASBA results during the first 4 and 6 weeks of treatment are significantly associated with the 12-week outcome. Blood RNA load change during weeks 4-6 may be informative to predict outcome at 12 weeks. While independent of serum GM, the kinetic change of circulating Aspergillus RNA appears to be well correlated with that of BG on some patient individuals. Monitoring blood Aspergillus RNA during the first 4-6 weeks of antifungal treatment may help assess therapeutic response. Combination of circulating Aspergillus RNA and BG may be a useful adjunct to assess response.
authors.affiliation: Public Health Research Institute, New Jersey Medical School-Rutgers Biomedical and Health Sciences, Newark, NJ 07103 zhaoy1@njms.rutgers.edu.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Public Health Research Institute, New Jersey Medical School-Rutgers Biomedical and Health Sciences, Newark, NJ 07103.
authors.forename: Padmaja
authors.initials: P
authors.lastname: Paderu
authors.affiliation: Merck and Co., Inc., North Wales, PA 19454.
authors.forename: Radha
authors.initials: R
authors.lastname: Railkar
authors.affiliation: Merck and Co., Inc., North Wales, PA 19454.
authors.forename: Cameron
authors.initials: C
authors.lastname: Douglas
authors.affiliation: Merck and Co., Inc., North Wales, PA 19454.
authors.forename: Robert
authors.initials: R
authors.lastname: Iannone
authors.affiliation: Merck and Co., Inc., North Wales, PA 19454.
authors.forename: Norah
authors.initials: N
authors.lastname: Shire
authors.affiliation: Public Health Research Institute, New Jersey Medical School-Rutgers Biomedical and Health Sciences, Newark, NJ 07103.
authors.forename: David S
authors.initials: DS
authors.lastname: Perlin
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use; D001230:Aspergillus / Q000235:genetics / Q000302:isolation & purification*; D015415:Biomarkers / Q000097:blood*; D016903:Drug Monitoring / Q000379:methods*; D005690:Galactose / Q000031:analogs & derivatives; D006801:Humans; D055744:Invasive Pulmonary Aspergillosis / Q000175:diagnosis* / Q000188:drug therapy; D008351:Mannans / Q000097:blood; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D011379:Prognosis; D011446:Prospective Studies; D011509:Proteoglycans; D012331:RNA, Fungal / Q000097:blood*; D013997:Time Factors; D016896:Treatment Outcome; D047071:beta-Glucans / Q000097:blood
chemical_list: D000935:Antifungal Agents; D015415:Biomarkers; D008351:Mannans; D011509:Proteoglycans; D012331:RNA, Fungal; D047071:beta-Glucans; C012990:galactomannan; C010770:polysaccharide-K; D005690:Galactose
keywords: Aspergillus RNA; NASBA; antifungal therapy; biomarker; invasive aspergillosis