Evaluation of a lateral flow immunochromatographic assay for detecting cryptococcal antigens in bronchoalveolar lavage fluid from HIV-negative patients with pulmonary cryptococcosis

Microbiol Spectr. 2026 Jan 6;14(1):e0108325. doi: 10.1128/spectrum.01083-25. Epub 2025 Dec 5.

Abstract

Cryptococcal antigen lateral flow immunochromatographic assay (CrAg-LFA) is extensively utilized for the diagnosis of cryptococcosis in serum and cerebrospinal fluid. However, its application in bronchoalveolar lavage fluid (BALF) has been relatively underexplored. This study aimed to assess the diagnostic performance of the CrAg-LFA in BALF from human immunodeficiency virus (HIV)-negative patients with pulmonary cryptococcosis (PC) over an 11-year period in a tertiary hospital in China and to compare it with serum samples. Among 514 clinically suspected PC patients at a tertiary hospital (January 2013 to February 2024), 42 were diagnosed with PC. BALF CrAg-LFA demonstrated a sensitivity of 88.1%, a specificity of 99.6%, a positive predictive value (PPV) of 94.9%, and a negative predictive value (NPV) of 98.9%. In contrast, the serum CrAg-LFA showed a sensitivity of 90.5%, a specificity of 99.6%, a PPV of 95.0%, and an NPV of 99.2%. The combination of BALF and serum CrAg-LFA enhanced both sensitivity and NPV to 100%, while maintaining high specificity (99.1%) and PPV (91.3%). One patient tested negative for CrAg-LFA in serum but positive in BALF. These findings underscore the excellent diagnostic accuracy of both specimen types for CrAg detection in HIV-negative PC patients and offer complementary diagnostic utility in specific clinical scenarios, such as cases with false-negative results. When bronchoscopy is indicated, adjunctive BALF CrAg testing can significantly enhance PC diagnosis, especially in patients with negative serum CrAg but strong clinical suspicion of infection.

Importance: This study demonstrates the significant diagnostic value of the cryptococcal antigen lateral flow immunochromatographic assay (CrAg-LFA) for pulmonary cryptococcosis (PC) in human immunodeficiency virus (HIV)-negative patients. We found that CrAg-LFA performed on bronchoalveolar lavage fluid (BALF) was highly effective, with a sensitivity of 88.1% and a specificity of 99.6%. Importantly, combining BALF and serum tests increased sensitivity and negative predictive value to 100%, providing a more reliable diagnostic approach. These findings highlight the utility of BALF CrAg-LFA in facilitating early and accurate PC diagnosis, which can significantly improve patient outcomes in non-HIV populations. This research offers critical insights into optimizing diagnostic strategies for this challenging condition.

Keywords: bronchoalveolar lavage fluid; cryptococcal antigen; lateral flow immunochromatographic assay; pulmonary cryptococcosis.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Antigens, Fungal* / analysis
  • Antigens, Fungal* / blood
  • Antigens, Fungal* / immunology
  • Bronchoalveolar Lavage Fluid* / chemistry
  • Bronchoalveolar Lavage Fluid* / microbiology
  • China
  • Chromatography, Affinity* / methods
  • Cryptococcosis* / diagnosis
  • Cryptococcosis* / immunology
  • Cryptococcosis* / microbiology
  • Cryptococcus* / immunology
  • Cryptococcus* / isolation & purification
  • Female
  • Humans
  • Immunoassay / methods
  • Lung Diseases, Fungal* / diagnosis
  • Lung Diseases, Fungal* / microbiology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Sensitivity and Specificity

Substances

  • Antigens, Fungal