Abstract

Chronic pulmonary aspergillosis (CPA) is a slow and progressive disease that develops in preexisting lung cavities of patients with tuberculosis sequelae, and it is associated with a high mortality rate. Serological tests such as double agar gel immunodiffusion test (DID) or counterimmunoelectrophoresis (CIE) test have been routinely used for CPA diagnosis in the absence of positive cultures. However, these tests have been replaced with enzyme-linked immunoassay (ELISA) and, a variety of methods. This systematic review compares ELISA accuracy to reference test (DID and/or CIE) accuracy in CPA diagnosis. It was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The study was registered in PROSPERO under the registration number CRD42016046057. We searched the electronic databases MEDLINE (PubMed), EMBASE (Elsevier), LILACS (VHL), Cochrane library, and ISI Web of Science. Gray literature was researched using Google Scholar and conference abstracts. We included articles with patients or serum samples from patients with CPA who underwent two serological tests: ELISA (index test) and IDD and/or CIE (reference test). We used the test accuracy as a result. Original articles were considered without a restriction of date or language. The pooled sensitivity, specificity, and summary receiver operating characteristic curves were estimated. We included 14 studies in the review, but only four were included in the meta-analysis. The pooled sensitivities and specificities were 0.93 and 0.97 for the ELISA test. These values were 0.64 and 0.99 for the reference test (DID and/or CIE). Analyses of summary receiver operating characteristic curves yielded 0.99 for ELISA and 0.99 for the reference test (DID and/or CIE). Our meta-analysis suggests that the diagnostic accuracy of ELISA is greater than the reference tests (DID and/or CIE) for early CPA detection.

Highlights

  • Chronic pulmonary aspergillosis (CPA) is a slow and progressive lung disease caused by Aspergillus spp. that develops in preexisting cavities in patients with chronic respiratory diseases

  • CPA presents with five clinical forms: aspergillus nodule; pulmonary simple aspergilloma; chronic cavitary pulmonary aspergillosis (CCPA), called complex aspergilloma; chronic fibrosing pulmonary aspergillosis (CFPA); and subacute invasive pulmonary aspergillosis (SAIA) [3]

  • More recent studies with commercial enzyme-linked immunoassay (ELISA) tests were included in the review, with the differences described

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Summary

Introduction

Chronic pulmonary aspergillosis (CPA) is a slow and progressive lung disease caused by Aspergillus spp. that develops in preexisting cavities in patients with chronic respiratory diseases. Antibodies against Aspergillus fumigatus were determined by detecting precipitins using double immunodiffusion test (DID) or counterimmunoelectrophoresis (CIE) technique [4, 8, 9] with a sensitivity of 89.3% [5] and a specificity of 100% [10] These techniques require much time, intense work, and relatively large A. fumigatus and patient serum extracts, and they only yield semiquantitative results [6]. Precipitation techniques have already been replaced by Aspergillus enzyme-linked immunosorbent assay (ELISA) IgG antibody detection test [12] This is the fastest and most sensitive test [13], producing quantitative results with less A. fumigatus extract and patient serum per test, and it is automated [6]. Considering the various methods for detecting Aspergillus antibodies, use of precipitation tests owing to their low cost, and absence of more precise options for serological diagnosis of CPA, this review of CPA serological diagnosis compared the performance of the precipitation tests with enzyme-linked immunoassay tests

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