Evaluation of low cryptococcal antigen titer as determined by the lateral flow assay in serum and cerebrospinal fluid among HIV-negative patients: a retrospective diagnostic accuracy study

Abstract Cryptococcosis is one of the most common opportunistic infections in both immunocompetent and immunocompromised hosts. Although the cryptococcal antigen (CrAg) lateral flow assay (LFA) has been widely used in clinical settings due to its high sensitivity and specificity, the diagnostic valu...

Full description

Saved in:
Bibliographic Details
Main Authors: Xuan Wang, Jia-Hui Cheng, Ling-Hong Zhou, Jun-Hao Zhu, Rui-Ying Wang, Hua-Zhen Zhao, Ying-Kui Jiang, Li-Ping Huang, Ching-Wan Yip, Chun-Xing Que, Min Zhu, Li-Ping Zhu
Format: Article
Language:English
Published: BMC 2020-03-01
Series:IMA Fungus
Subjects:
Online Access:http://link.springer.com/article/10.1186/s43008-020-00028-w
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832569391601942528
author Xuan Wang
Jia-Hui Cheng
Ling-Hong Zhou
Jun-Hao Zhu
Rui-Ying Wang
Hua-Zhen Zhao
Ying-Kui Jiang
Li-Ping Huang
Ching-Wan Yip
Chun-Xing Que
Min Zhu
Li-Ping Zhu
author_facet Xuan Wang
Jia-Hui Cheng
Ling-Hong Zhou
Jun-Hao Zhu
Rui-Ying Wang
Hua-Zhen Zhao
Ying-Kui Jiang
Li-Ping Huang
Ching-Wan Yip
Chun-Xing Que
Min Zhu
Li-Ping Zhu
author_sort Xuan Wang
collection DOAJ
description Abstract Cryptococcosis is one of the most common opportunistic infections in both immunocompetent and immunocompromised hosts. Although the cryptococcal antigen (CrAg) lateral flow assay (LFA) has been widely used in clinical settings due to its high sensitivity and specificity, the diagnostic value of a low CrAg LFA titers remains unclear. In this study, we performed a retrospective analysis of 149 HIV-negative patients with low CrAg LFA titers (≤1:10) in a Chinese tertiary hospital from January 2013 to December 2017, to evaluate the diagnostic value of low CrAg LFA titers in serum and cerebrospinal fluid (CSF) at different thresholds. Sensitivity and specificity of low CrAg LFA titers in patients with definitive diagnoses of cryptococcosis were 39.6% (95% CI, 29.7–50.1%) and 100% (95% CI, 69.2–100%), respectively, at a threshold of 1:10 in serum. A sensitivity of 72.9% (95% CI, 62.9–81.5%) and a decreased specificity of 70.0% (95% CI, 34.8–93.3%) were observed at a threshold of 1:5 in serum. No false-positive cases were identified in patients with low CrAg titers in CSF and all positive predictive values (PPVs) were 100%. Among the cases with low serum CrAg titers, lumbar puncture was performed in 97 patients and positive CSF CrAg titers were reported in 6 patients. In conclusion, the results of this study imply that low CrAg LFA titer, either in serum or CSF, is crucial for early diagnosis of cryptococcosis in HIV-negative patients, and lumbar puncture is recommended to be performed routinely for CSF testing when a positive low serum titer is reported. Cryptococcal meningitis should be considered seriously when the CSF CrAg titer is positive.
format Article
id doaj-art-6084f9336506474d83cfd591a6fcfebd
institution Kabale University
issn 2210-6359
language English
publishDate 2020-03-01
publisher BMC
record_format Article
series IMA Fungus
spelling doaj-art-6084f9336506474d83cfd591a6fcfebd2025-02-02T21:34:35ZengBMCIMA Fungus2210-63592020-03-011111710.1186/s43008-020-00028-wEvaluation of low cryptococcal antigen titer as determined by the lateral flow assay in serum and cerebrospinal fluid among HIV-negative patients: a retrospective diagnostic accuracy studyXuan Wang0Jia-Hui Cheng1Ling-Hong Zhou2Jun-Hao Zhu3Rui-Ying Wang4Hua-Zhen Zhao5Ying-Kui Jiang6Li-Ping Huang7Ching-Wan Yip8Chun-Xing Que9Min Zhu10Li-Ping Zhu11Department of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan UniversityDivision of Mycology, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan UniversityDivision of Mycology, Huashan Hospital, Shanghai Medical College, Fudan UniversityDepartment of Infectious Diseases, Huashan Hospital, Shanghai Medical College, Fudan UniversityAbstract Cryptococcosis is one of the most common opportunistic infections in both immunocompetent and immunocompromised hosts. Although the cryptococcal antigen (CrAg) lateral flow assay (LFA) has been widely used in clinical settings due to its high sensitivity and specificity, the diagnostic value of a low CrAg LFA titers remains unclear. In this study, we performed a retrospective analysis of 149 HIV-negative patients with low CrAg LFA titers (≤1:10) in a Chinese tertiary hospital from January 2013 to December 2017, to evaluate the diagnostic value of low CrAg LFA titers in serum and cerebrospinal fluid (CSF) at different thresholds. Sensitivity and specificity of low CrAg LFA titers in patients with definitive diagnoses of cryptococcosis were 39.6% (95% CI, 29.7–50.1%) and 100% (95% CI, 69.2–100%), respectively, at a threshold of 1:10 in serum. A sensitivity of 72.9% (95% CI, 62.9–81.5%) and a decreased specificity of 70.0% (95% CI, 34.8–93.3%) were observed at a threshold of 1:5 in serum. No false-positive cases were identified in patients with low CrAg titers in CSF and all positive predictive values (PPVs) were 100%. Among the cases with low serum CrAg titers, lumbar puncture was performed in 97 patients and positive CSF CrAg titers were reported in 6 patients. In conclusion, the results of this study imply that low CrAg LFA titer, either in serum or CSF, is crucial for early diagnosis of cryptococcosis in HIV-negative patients, and lumbar puncture is recommended to be performed routinely for CSF testing when a positive low serum titer is reported. Cryptococcal meningitis should be considered seriously when the CSF CrAg titer is positive.http://link.springer.com/article/10.1186/s43008-020-00028-wCryptococcosisMeningitisLow cryptococcal antigen titerLateral flow assayDiagnostic accuracy
spellingShingle Xuan Wang
Jia-Hui Cheng
Ling-Hong Zhou
Jun-Hao Zhu
Rui-Ying Wang
Hua-Zhen Zhao
Ying-Kui Jiang
Li-Ping Huang
Ching-Wan Yip
Chun-Xing Que
Min Zhu
Li-Ping Zhu
Evaluation of low cryptococcal antigen titer as determined by the lateral flow assay in serum and cerebrospinal fluid among HIV-negative patients: a retrospective diagnostic accuracy study
IMA Fungus
Cryptococcosis
Meningitis
Low cryptococcal antigen titer
Lateral flow assay
Diagnostic accuracy
title Evaluation of low cryptococcal antigen titer as determined by the lateral flow assay in serum and cerebrospinal fluid among HIV-negative patients: a retrospective diagnostic accuracy study
title_full Evaluation of low cryptococcal antigen titer as determined by the lateral flow assay in serum and cerebrospinal fluid among HIV-negative patients: a retrospective diagnostic accuracy study
title_fullStr Evaluation of low cryptococcal antigen titer as determined by the lateral flow assay in serum and cerebrospinal fluid among HIV-negative patients: a retrospective diagnostic accuracy study
title_full_unstemmed Evaluation of low cryptococcal antigen titer as determined by the lateral flow assay in serum and cerebrospinal fluid among HIV-negative patients: a retrospective diagnostic accuracy study
title_short Evaluation of low cryptococcal antigen titer as determined by the lateral flow assay in serum and cerebrospinal fluid among HIV-negative patients: a retrospective diagnostic accuracy study
title_sort evaluation of low cryptococcal antigen titer as determined by the lateral flow assay in serum and cerebrospinal fluid among hiv negative patients a retrospective diagnostic accuracy study
topic Cryptococcosis
Meningitis
Low cryptococcal antigen titer
Lateral flow assay
Diagnostic accuracy
url http://link.springer.com/article/10.1186/s43008-020-00028-w
work_keys_str_mv AT xuanwang evaluationoflowcryptococcalantigentiterasdeterminedbythelateralflowassayinserumandcerebrospinalfluidamonghivnegativepatientsaretrospectivediagnosticaccuracystudy
AT jiahuicheng evaluationoflowcryptococcalantigentiterasdeterminedbythelateralflowassayinserumandcerebrospinalfluidamonghivnegativepatientsaretrospectivediagnosticaccuracystudy
AT linghongzhou evaluationoflowcryptococcalantigentiterasdeterminedbythelateralflowassayinserumandcerebrospinalfluidamonghivnegativepatientsaretrospectivediagnosticaccuracystudy
AT junhaozhu evaluationoflowcryptococcalantigentiterasdeterminedbythelateralflowassayinserumandcerebrospinalfluidamonghivnegativepatientsaretrospectivediagnosticaccuracystudy
AT ruiyingwang evaluationoflowcryptococcalantigentiterasdeterminedbythelateralflowassayinserumandcerebrospinalfluidamonghivnegativepatientsaretrospectivediagnosticaccuracystudy
AT huazhenzhao evaluationoflowcryptococcalantigentiterasdeterminedbythelateralflowassayinserumandcerebrospinalfluidamonghivnegativepatientsaretrospectivediagnosticaccuracystudy
AT yingkuijiang evaluationoflowcryptococcalantigentiterasdeterminedbythelateralflowassayinserumandcerebrospinalfluidamonghivnegativepatientsaretrospectivediagnosticaccuracystudy
AT lipinghuang evaluationoflowcryptococcalantigentiterasdeterminedbythelateralflowassayinserumandcerebrospinalfluidamonghivnegativepatientsaretrospectivediagnosticaccuracystudy
AT chingwanyip evaluationoflowcryptococcalantigentiterasdeterminedbythelateralflowassayinserumandcerebrospinalfluidamonghivnegativepatientsaretrospectivediagnosticaccuracystudy
AT chunxingque evaluationoflowcryptococcalantigentiterasdeterminedbythelateralflowassayinserumandcerebrospinalfluidamonghivnegativepatientsaretrospectivediagnosticaccuracystudy
AT minzhu evaluationoflowcryptococcalantigentiterasdeterminedbythelateralflowassayinserumandcerebrospinalfluidamonghivnegativepatientsaretrospectivediagnosticaccuracystudy
AT lipingzhu evaluationoflowcryptococcalantigentiterasdeterminedbythelateralflowassayinserumandcerebrospinalfluidamonghivnegativepatientsaretrospectivediagnosticaccuracystudy