Evaluation of the LDBio ICT IgG/IgM lateral flow assay versus the Bordier Elisa assay for the diagnosis of chronic pulmonary aspergillosis in Nigeria

Abstract

The detection of anti-Aspergillus antibodies is key for diagnosing chronic pulmonary aspergillosis (CPA). Available techniques are limited and pose a considerable challenge in resource-limited settings. The objective of this study was to evaluate the performance of the point-of-care test LDBio ICT IgG/IgM lateral flow assay (LDBio) versus that of the Bordier Elisa assay in a field study in Nigeria. Of the 97 serum samples tested in the CPA patient group, 71 tested positive by the LDBio assay with 69.4% sensitivity. In the non-CPA group, 286 of the 289 sera tested negative by the LDBio assay with 98.7% specificity. The Bordier test was positive for 97 of the 97 CPA serum samples tested, showing 100% sensitivity, significantly different from the LDBio test in detecting Aspergillus antibodies (P < 0.0001). However, there was no significant difference in the specificity between the two tests (P = 0.617). The results were in agreement for 353 of the 386 samples tested (91.5%), with a Cohen's kappa coefficient of 0.75, indicating substantial agreement between the LDBio and Bordier test results. The LDBio lateral flow assay (LFA) test is a simple and rapid point-of-care test that can be used in field studies in which the Elisa test is not available. The lower sensitivity of the LDBio LFA in our field study could have been due to A. fumigatus being the species involved in only 50%-60% of cases in Nigeria, with A. flavus being more frequent than in Northern countries.IMPORTANCEAvailable techniques for the detection of Aspergillus IgG are limited and pose a considerable challenge in resource-limited settings in terms of affordability, skilled personnel, equipment, and a regular power supply. A point-of-care test would address most of these challenges. The LDBio lateral flow assay (LFA) test is a simple and rapid point-of-care test that can be used in field studies in which the Elisa test is not available. When combined with clinical features, the LFA can be used as a screening tool for chronic pulmonary aspergillosis in settings such as ours; however, a lower sensitivity was observed compared to the Elisa.

Keywords: Aspergillus flavus; Aspergillus fumigatus; antibodies; chronic pulmonary aspergillosis; point-of-care diagnosis.

Fig 1

Chest X-ray findings and Aspergillus IgG distribution according to CPA type. (A) Prevalence of CPA radiological features. Prevalence of only one feature, two, three, and all four of cavitation (Cavi), fibrosis (Fibr), fungal ball (Fung), and pleural thickening (Pleu) were 45.4%, 35.1%, 15.5%, and 4.1% respectively. (B) Distribution of Aspergillus-specific IgG levels in type of CPA. Aspergillus IgG levels during chronic cavitary pulmonary aspergillosis (CCPA), chronic fibrosing pulmonary aspergillosis (CFPA), and pulmonary aspergilloma (PA) were 1.689 (0.992–2.206) AU/mL, 1.154 (0.884–3.034) AU/mL, and 2.01 (0.888–2.856) AU/mL, respectively. (C) Distribution of Aspergillus IgG levels according to the species: Aspergillus flavus; IgG level = 1.303 (1.024–2.036) AU/mL, Aspergillus fumigatus; IgG level = 1.781 (1.154–1.922) AU/mL, Aspergillus niger; IgG level = 0.933 (0.872–1.855) AU/mL, and Aspergillus IgG level for two or three combination of Aspergillus species (Com) = 1.089 (0.873–2.082) AU/mL. (D) Distribution of Aspergillus-specific IgG in the stratification of treatment type and type of CPA. Aspergillus-specific IgG level in post-TB group = 1.446 (0.976–2.168) AU/mL, in retreatment group = 1.367 (0.874–2.197) AU/mL.

Fig 2

Diagnostic results of Bordier test kits (the gold standard) and the LDBio test (Index test). (A) Distribution of the frequency of positive results for the Bordier (97 CPA) and LDBio (71 CPA) tests. (B) Distribution of the frequency of misclassification for the LDBio test for CPA (29 misclassified as non-CPA) and non-CPA (three misclassified as CPA) patients. (C) Distribution of the frequency of Bordier Aspergillus-specific IgG titers for the sera of 386 patients categorized as low (0–0.49 AU/mL), medium (0.5–0.99 AU/mL), or high (≥1.0 AU/mL) tested with the LDBio Aspergillus ICT test. (D) Distribution of the frequency of Bordier Aspergillus IgG titers for cutoffs of 0.8, 0.9, and 1.0 AU/mL for 386 patients tested with the LDBio test.

Fig 3

Receiver operating characteristic (ROC) curves with different positivity thresholds for the Bordier and LDBio tests. The Bordier test showed a sensitivity of 100% (95% CI, 96.3%–100%), a specificity of 99.7% (95% CI, 98.1%–99.9%), and an accuracy of 99.7% (95% CI, 99.6%–99.9%). The LDBio test showed a sensitivity of 69.4% (95% CI, 59.3%–78.3%), a specificity of 98.7% (95% CI, 96.7%–99.8%), and an accuracy of 91.5% (95% CI, 88.2%–94.0%).