The diagnostic value of cryptococcal antigen lateral flow immunochromatographic assay in bronchoalveolar lavage fluid among patients with pulmonary cryptococcosis_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

 ZENG Huiqing ^1,2 , CAI Xueying ¹ , ZHANG Xiaobin ¹ , YANG Dongyong ³ , LIN Li ⁴ , CHEN Meijun ⁵ , GUO Weifeng ⁶ , ZHU Sihong ² , CHEN Xiangxing ² , CHEN Xiaorong ² , HUANG Yemei ¹

1. Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, P. R. China;
2. Department of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian 350001, P. R. China;
3. Department of Pulmonary and Critical Care Medicine, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362006, P. R. China;
4. Department of Pulmonary and Critical Care Medicine, Zhangzhou Municipal Hospital of Fujian Medical University, Zhangzhou, Fujian 363002, P. R. China;
5. Clinical Laboratory Center, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, P. R. China;
6. Department of Pulmonary and Critical Care Medicine, Quanzhou First Hospital of Fujian Medical University, Quanzhou, Fujian 362003, P. R. China;

Corresponding?author：

ZENG Huiqing, Email: 13606080893@139.com

Keywords：

Lateral flow immunochromatographic assay; Cryptococcal antigen; Bronchoalveolar lavage fluid; Pulmonary cryptococcosis

DOI：

10.7507/1671-6205.201902006

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Objective To evaluate the diagnostic value of cryptococcal antigen lateral flow immunochromatographic assay (CrAg-LFA) in bronchoalveolar lavage fluid (BALF) among pulmonary cryptococcosis (PC) patients.Methods Patients from the Zhongshan Hospital, Xiamen University, Zhangzhou Municipal Hospital of Fujian Medical University, Second Affiliated Hospital of Fujian Medical University, and Quanzhou First Hospital of Fujian Medical University were enrolled prospectively from March 2015 to October 2018. They were confirmed without human immunodeficiency virus infection and were divided into non-PC group (236 cases) and PC group (72 cases). The PC was definitely diagnosed by histopathological evidence from lung biopsy. The CrAg-LFA and culture were performed in both the serum and BALF among the enrolled patients.Results Among 72 PC patients, 54 had a positive serum CrAg-LFA, 1 had positive serum culture; 67 patients had a positive BALF CrAg-LFA, 9 had positive BALF culture. Among the non-PC group, only 1 patient had a weak positive serum CrAg-LFA, none had positive serum culture of PC; 236 cases non-PC patients underwent BALF CrAg-LFA detection, none had a positive BALF CrAg-LFA; none of the 121 cases who had BALF culture yielded a positive result in PC. The sensitivity, specificity, positive predicted value, and negative predicted value in serum were 75.0%, 99.6%, 98.2%, and 92.9%, respectively. Those above mentioned values in the BALF yielded 93.6%, 100.0%, 100.0%, and 97.9%, respectively. Among the PC group, the sensitivity was higher in BALF than that in serum (χ²=8.745, P<0.05).Conclusions The CrAg-LFA is a simple and rapid diagnostic method for PC. The diagnostic value of CrAg-LFA in the BALF is superior to that in serum and fungal culture among the PC patients. The positive BALF CrAg-LFA result is consistent with mycological positive results.

Citation： ZENG Huiqing, CAI Xueying, ZHANG Xiaobin, YANG Dongyong, LIN Li, CHEN Meijun, GUO Weifeng, ZHU Sihong, CHEN Xiangxing, CHEN Xiaorong, HUANG Yemei. The diagnostic value of cryptococcal antigen lateral flow immunochromatographic assay in bronchoalveolar lavage fluid among patients with pulmonary cryptococcosis. Chinese Journal of Respiratory and Critical Care Medicine, 2020, 19(3): 258-263. doi: 10.7507/1671-6205.201902006 Copy

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2.	Boulware DR, Rolfes MA, Rajasingham R, et al. Multisite validation of cryptococcal antigen lateral flow assay and quantification by laser thermal contrast. Emerg Infect Dis, 2014, 20(1): 45-53.
3.	Vijayan T, Chiller T, Klausner JD. Sensitivity and specificity of a new cryptococcal antigen lateral flow assay in serum and cerebrospinal fluid. MLO Med Lab Obs, 2013, 45(3): 16-18, 20.
4.	Jenks JD, Mehta SR, Taplitz R, et al. Bronchoalveolar lavage Aspergillus Galactomannan lateral flow assay versus Aspergillus-specific lateral flow device test for diagnosis of invasive pulmonary Aspergillosis in patients with hematological malignancies. J Infect, 2019, 78(3): 249-259.
5.	Jenks JD, Mehta SR, Taplitz R, et al. Point-of-care diagnosis of invasive aspergillosis in nonneutropenic patients: Aspergillus Galactomannan Lateral Flow Assay versus Aspergillus--specific Lateral Flow Device test in bronchoalveolar lavage. Mycoses, 2019, 62(3): 230-236.
6.	中華醫學會呼吸分會. 肺真菌病診斷與治療專家共識. 中華結核和呼吸雜志, 2007, 3(11): 812-834.
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9.	王麗芳, 施毅, 丁媛, 等. 肺隱球菌病 65 例回顧分析. 中華結核和呼吸雜志, 2014, 10(10): 764-768.
10.	Thomaz DY, Grenfell RC, Vidal MS, et al. Does the capsule interfere with performance of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of Ctyptococcus neoformans and Cryptococcus gattii. J Clin Microbiol, 2016, 54(2): 474-477.
11.	黃佳斯, 石磊, 唐愛國, 等. 膠體金免疫層析法檢測血清隱球菌抗原在肺隱球菌病診斷中的應用價值. 臨床檢驗雜志, 2017, 35(7): 518-520.
12.	付雅捷, 楊青. 隱球菌莢膜多糖抗原膠體金法在肺隱球菌病診斷中的應用. 預防醫學, 2017, 29(5): 539-541.
13.	Huang HR, Fan LC, Rajbanshi B, et al. Evaluation of a new eryptococeal antigen lateral flow immunoassay in serum, cerebrospinal fluid and urine for the diagnosis of cryptococcosis: a meta-analysis and systematic review. PLoS One, 2015, 10(5): e0127117.
14.	陳櫟江, 吳慶, 徐春泉, 等. 血清隱球菌莢膜多糖抗原檢測在肺隱球菌病中的早期診斷價值. 中國抗生素雜志, 2018, 43(10): 1248-1251.
15.	Singh N, Alexander BD, Lortholary O, et al. Pulmonary. cryptococcosis in solid organ transplant recipients: clinical relevance of serum cryptococcal antigen. Clin Infect Dis, 2008, 46(2): e12-18.
16.	Jitmuang A, Panackal AA, Williamson PR, et al. Performance of the cryptococcal antigen lateral flow assay in non-HIV-related cryptococcosis. J Clin Microbiol, 2016, 54(2): 460-463.
17.	中華醫學會呼吸病學分會. 肺部感染性疾病支氣管肺泡灌洗病原體檢測中國專家共識(2017 年版). 中華結核和呼吸雜志, 2017, 40(8): 578-583.
18.	Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect, 2018, 24(Suppl 1): e1-e38.
19.	Guo YL, Chen YQ, Wang K, et al. Accuracy galactomannan in diagnosing invasive aspergillosis: a bivariate metaanalysis and systematic review. Chest, 2010, 138(4): 817-824.
20.	Williams DA, Kiiza T, Kwizera R, et al. Evaluation of fingerstick cryptococcal antigen lateral flow assay in HIV-infected persons: a diagnostic accuracy study. Clin Infect Dis, 2015, 61(3): 464-467.
21.	Opota O, Desgraz B, Kenfak A, et al. Cryptococcus neoformans meningitis with negative eryptococcal antigen: evaluation of a new immunochromatographic detection assay. New Microbes New Infect, 2014, 4: 1-4.

1. 葉楓, 謝佳星, 李少強, 等. 非免疫缺陷者肺隱球菌病 110 例臨床分析. 國際呼吸雜志, 2014, 34(2): 81-86.
2. Boulware DR, Rolfes MA, Rajasingham R, et al. Multisite validation of cryptococcal antigen lateral flow assay and quantification by laser thermal contrast. Emerg Infect Dis, 2014, 20(1): 45-53.
3. Vijayan T, Chiller T, Klausner JD. Sensitivity and specificity of a new cryptococcal antigen lateral flow assay in serum and cerebrospinal fluid. MLO Med Lab Obs, 2013, 45(3): 16-18, 20.
4. Jenks JD, Mehta SR, Taplitz R, et al. Bronchoalveolar lavage Aspergillus Galactomannan lateral flow assay versus Aspergillus-specific lateral flow device test for diagnosis of invasive pulmonary Aspergillosis in patients with hematological malignancies. J Infect, 2019, 78(3): 249-259.
5. Jenks JD, Mehta SR, Taplitz R, et al. Point-of-care diagnosis of invasive aspergillosis in nonneutropenic patients: Aspergillus Galactomannan Lateral Flow Assay versus Aspergillus--specific Lateral Flow Device test in bronchoalveolar lavage. Mycoses, 2019, 62(3): 230-236.
6. 中華醫學會呼吸分會. 肺真菌病診斷與治療專家共識. 中華結核和呼吸雜志, 2007, 3(11): 812-834.
7. 徐禮裕, 柳德靈, 余英豪, 等. 病理確診的肺隱球菌病 38 例臨床分析. 中華結核和呼吸雜志, 2011, 34(9): 653-656.
8. 劉又寧, 佘丹陽, 孫鐵英, 等. 中國 1998 年至 2007 年臨床確診的肺真菌病患者的多中心回顧性調查. 中華結核和呼吸雜志, 2011, 34(2): 86-90.
9. 王麗芳, 施毅, 丁媛, 等. 肺隱球菌病 65 例回顧分析. 中華結核和呼吸雜志, 2014, 10(10): 764-768.
10. Thomaz DY, Grenfell RC, Vidal MS, et al. Does the capsule interfere with performance of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of Ctyptococcus neoformans and Cryptococcus gattii. J Clin Microbiol, 2016, 54(2): 474-477.
11. 黃佳斯, 石磊, 唐愛國, 等. 膠體金免疫層析法檢測血清隱球菌抗原在肺隱球菌病診斷中的應用價值. 臨床檢驗雜志, 2017, 35(7): 518-520.
12. 付雅捷, 楊青. 隱球菌莢膜多糖抗原膠體金法在肺隱球菌病診斷中的應用. 預防醫學, 2017, 29(5): 539-541.
13. Huang HR, Fan LC, Rajbanshi B, et al. Evaluation of a new eryptococeal antigen lateral flow immunoassay in serum, cerebrospinal fluid and urine for the diagnosis of cryptococcosis: a meta-analysis and systematic review. PLoS One, 2015, 10(5): e0127117.
14. 陳櫟江, 吳慶, 徐春泉, 等. 血清隱球菌莢膜多糖抗原檢測在肺隱球菌病中的早期診斷價值. 中國抗生素雜志, 2018, 43(10): 1248-1251.
15. Singh N, Alexander BD, Lortholary O, et al. Pulmonary. cryptococcosis in solid organ transplant recipients: clinical relevance of serum cryptococcal antigen. Clin Infect Dis, 2008, 46(2): e12-18.
16. Jitmuang A, Panackal AA, Williamson PR, et al. Performance of the cryptococcal antigen lateral flow assay in non-HIV-related cryptococcosis. J Clin Microbiol, 2016, 54(2): 460-463.
17. 中華醫學會呼吸病學分會. 肺部感染性疾病支氣管肺泡灌洗病原體檢測中國專家共識(2017 年版). 中華結核和呼吸雜志, 2017, 40(8): 578-583.
18. Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect, 2018, 24(Suppl 1): e1-e38.
19. Guo YL, Chen YQ, Wang K, et al. Accuracy galactomannan in diagnosing invasive aspergillosis: a bivariate metaanalysis and systematic review. Chest, 2010, 138(4): 817-824.
20. Williams DA, Kiiza T, Kwizera R, et al. Evaluation of fingerstick cryptococcal antigen lateral flow assay in HIV-infected persons: a diagnostic accuracy study. Clin Infect Dis, 2015, 61(3): 464-467.
21. Opota O, Desgraz B, Kenfak A, et al. Cryptococcus neoformans meningitis with negative eryptococcal antigen: evaluation of a new immunochromatographic detection assay. New Microbes New Infect, 2014, 4: 1-4.

Chinese Journal of Respiratory and Critical Care Medicine

The diagnostic value of cryptococcal antigen lateral flow immunochromatographic assay in bronchoalveolar lavage fluid among patients with pulmonary cryptococcosis

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