Inter-Laboratory and Inter-Study Reproducibility of a Novel Lateral-Flow Device and the Influence of Antifungal Therapy on the Detection of Invasive Pulmonary Aspergillosis.
J Clin Microbiol. 2012 Nov 21;
Authors: Wiederhold NP, Najvar LK, Bocanegra R, Kirkpatrick WR, Patterson TF, Thornton CR
Lateral-flow devices (LFD) have gained interest as potential point-of-care assays for the diagnosis of infectious diseases. Our objective was to evaluate the inter-laboratory and inter-study reproducibility and the effects of antifungal therapy on a LFD developed for invasive pulmonary aspergillosis (IPA) detection. An established neutropenic guinea pig model of IPA caused by Aspergillus fumigatus was used. At predetermined time points (1 hr, 3, 5, and 7 days post-inoculation) blood and BAL fluid were collected from infected and uninfected animals. In a separate experiment, guinea pigs were treated with posaconazole (10 mg/kg PO BID), voriconazole (10 mg/kg PO BID), liposomal amphotericin B (10 mg/kg IP QD), or caspofungin (2 mg/kg IP QD), and samples were collected on days 7 and 11. Each laboratory independently evaluated the IgG monoclonal antibody-based LFD. Galactomannan and (1→3)-β-D-glucan were also measured using commercially available kits. Good inter-laboratory agreement was observed with the LFD as 97% (32/33) of the serum and 78.8% (26/33) of the BAL samples from infected animals were in agreement. Good inter-study agreement was also observed. The serum sensitivity of each surrogate marker assay was reduced in animals treated with antifungals. In contrast, these markers remained elevated within the BAL fluids of treated animals, which was consistent with the fungal burden and histopathology results. These results demonstrate that the LFD assay is reproducible between different laboratories and studies. However, the sensitivity of this assay and other markers of IPA may be reduced within the serum in the presence of antifungal therapy.
PMID: 23175252 [PubMed - as supplied by publisher]