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

doi:10.1128/JCM.01975-18

A Simple Microfluidic Assay for Diagnosing Tuberculous Meningitis in HIV-Uninfected Patients

J Clin Microbiol. 2019 Apr 26;57(5):e01975-18. doi: 10.1128/JCM.01975-18. Print 2019 May.

Authors

Affiliations

¹ Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
² Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
³ Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
⁴ Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea [email protected] [email protected].
⁵ Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea [email protected] [email protected].

^# Contributed equally.

Abstract

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.

Keywords: SLIM assay; Xpert MTB/RIF; tuberculous meningitis.

Publication types

Evaluation Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
DNA, Bacterial / genetics
Female
HIV Infections
Humans
Imidoesters
Male
Microfluidics / methods*
Middle Aged
Molecular Diagnostic Techniques
Mycobacterium tuberculosis
Prospective Studies
Sensitivity and Specificity
Tertiary Care Centers
Tuberculosis, Meningeal / cerebrospinal fluid
Tuberculosis, Meningeal / diagnosis*

Substances

DNA, Bacterial
Imidoesters