A simple microfluidic assay for diagnosing tuberculous meningitis in HIV-uninfected patients

Joung Ha Park, Choong Eun Jin, Bonhan Koo, Ji Soo Kwon, Hye Hee Cha, Ji Yeun Kim, Geun Su Noh, Yong Seo Koo, Sang Beom Jeon, Sang Ahm Lee, Yong Shin, Sung Han Kim

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10 Citations (Scopus)


We evaluated the diagnostic performance of a simple and label-free pathogen enrichment method using homobifunctional imidoesters (HI) and a microfluidic system, called the SLIM assay, followed by real-time PCR from cerebrospinal fluid (CSF) in human immunodeficiency virus (HIV)-uninfected patients with suspected tuberculous meningitis (TBM). Patients with suspected TBM were prospectively enrolled in a tertiary hospital in an intermediate tuberculosis (TB)-burden country during a 30-month period. TBM was classified according to the uniform case definition. Definite and probable TBM were regarded as the reference standards for TBM, and possible TBM and not-TBM as the reference standards for not-TBM. Of 72 HIV-uninfected patients with suspected TBM, 10 were diagnosed with definite (n=2) and probable (n=8) TBM by the uniform case definition. The sensitivity of the SLIM assay was 100% (95% confidence interval [CI], 69 to 100%) compared with definite or probable TBM, and it was superior to those of mycobacterial culture (20% [95% CI, 3 to 56%]) and the Xpert MTB/RIF assay (0% [95% CI, 0 to 31%]). Of 21 possible TBM and 41 not-TBM patients by the uniform case definition, 5 possible TBM and no not-TBM patients gave positive results in the SLIM assay. The specificity of the SLIM assay was 92% (95% CI, 82 to 97%; 5/62). We demonstrated that the SLIM assay had a very high sensitivity and specificity with small samples of 10 cases of definite or probable TBM. Further studies are needed to confirm this finding and to compare the SLIM assay with mycobacterial culture, Xpert MTB/RIF, and Xpert MTB/ RIF Ultra assays in a larger prospective cohort of patients with suspected TBM, including both HIV-infected and HIV-uninfected cases.

Original languageEnglish
Article numbere01975-18
JournalJournal of Clinical Microbiology
Issue number5
Publication statusPublished - 2019 May

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (grants NRF-2018R1D1A1A09082099 and NRF-2017R1A2B4005288) and was also supported by grants (2018-7034 and 2018-7040) from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea. We have no potential conflicts of interest.

Publisher Copyright:
© 2019 American Society for Microbiology. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)


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