Disease spectrum and prognostic factors in patients treated for tuberculous meningitis in Shaanxi province, China

Ting Wang; Meng-Yan Li; Xin-Shan Cai; Qiu-Sheng Cheng; Ze Li; Ting-Ting Liu; Lin-Fu Zhou; Hong-Hao Wang; Guo-Dong Feng; Ben J Marais; Gang Zhao

doi:10.3389/fmicb.2024.1374458

Disease spectrum and prognostic factors in patients treated for tuberculous meningitis in Shaanxi province, China

Front Microbiol. 2024 May 17:15:1374458. doi: 10.3389/fmicb.2024.1374458. eCollection 2024.

Authors

Ting Wang^#¹, Meng-Yan Li^#¹, Xin-Shan Cai^#², Qiu-Sheng Cheng¹, Ze Li¹, Ting-Ting Liu³, Lin-Fu Zhou⁴, Hong-Hao Wang¹, Guo-Dong Feng⁵, Ben J Marais⁶, Gang Zhao^{3

4}

Affiliations

¹ Department of Neurology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
² Department of Clinical Laboratory, Guangzhou Chest Hospital, Guangzhou, China.
³ Department of Neurology, Xijing Hospital, The Air Force Medical University, Xi'an, China.
⁴ Department of Neurology, Northwestern University School of Medicine, Xi'an, China.
⁵ Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.
⁶ Sydney Infectious Diseases Institute (Sydney ID) and the WHO Collaborating Centre in Tuberculosis, University of Sydney, Sydney, NSW, Australia.

^# Contributed equally.

Abstract

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) and can be difficult to diagnose and treat. We aimed to describe the clinical presentation, diagnosis, disease spectrum, outcome, and prognostic factors of patients treated for TBM in China.

Methods: A multicenter retrospective study was conducted from 2009 to 2019 enrolling all presumptive TBM patients referred to Xijing tertiary Hospital from 27 referral centers in and around Shaanxi province, China. Patients with clinical features suggestive of TBM (abnormal CSF parameters) were included in the study if they had adequate baseline information to be classified as "confirmed," "probable," or "possible" TBM according to international consensus TBM criteria and remained in follow-up. Patients with a confirmed alternative diagnosis or severe immune compromise were excluded. Clinical presentation, central nervous system imaging, cerebrospinal fluid (CSF) results, TBM score, and outcome-assessed using the modified Barthel disability index-were recorded and compared.

Findings: A total of 341 presumptive TBM patients met selection criteria; 63 confirmed TBM (25 culture positive, 42 Xpert-MTB/RIF positive), 66 probable TBM, 163 possible TBM, and 49 "not TBM." Death was associated with BMRC grade III (OR = 5.172; 95%CI: 2.298-11.641), TBM score ≥ 15 (OR = 3.843; 95%CI: 1.372-10.761), age > 60 years (OR = 3.566; 95%CI: 1.022-12.442), and CSF neutrophil ratio ≥ 25% (OR = 2.298; 95%CI: 1.027-5.139). Among those with confirmed TBM, nearly one-third (17/63, 27.0%) had a TBM score < 12; these patients exhibited less classic meningitis symptoms and signs and had better outcomes compared with those with a TBM score ≥ 12. In this group, signs of disseminated/miliary TB (OR = 12.427; 95%CI: 1.138-135.758) and a higher TBM score (≥15, OR = 8.437; 95%CI: 1.328-53.585) were most strongly associated with death.

Conclusion: TBM patients who are older (>60 years) have higher TBM scores or CSF neutrophil ratios, have signs of disseminated/miliary TB, and are at greatest risk of death. In general, more effort needs to be done to improve early diagnosis and treatment outcome in TBM patients.

Keywords: CSF; diagnostic; disease spectrum; prognostic factors; tuberculous meningitis.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (No: 82101430) to TW, the Science and Technology Projects in Guangzhou to TW (No: 202201010610), the start-up funding for doctoral research of Guangzhou First People’s Hospital (No: KY09050006) to TW, the Science and Technology Projects in Guangzhou (No: 202102080086) to MY-L and the National Natural Science Foundation of China (81371334) to GZ.