Dataset Information

High rate of drug resistance among tuberculous meningitis cases in Shaanxi province, China.

ABSTRACT: The clinical and mycobacterial features of tuberculous meningitis (TBM) cases in China are not well described; especially in western provinces with poor tuberculosis control. We prospectively enrolled patients in whom TBM was considered in Shaanxi Province, northwestern China, over a 2-year period (September 2010 to December 2012). Cerebrospinal fluid specimens were cultured for Mycobacterium tuberculosis; with phenotypic and genotypic drug susceptibility testing (DST), as well as genotyping of all positive cultures. Among 350 patients included in the study, 27 (7.7%) had culture-confirmed TBM; 84 (24.0%) had probable and 239 (68.3%) had possible TBM. DST was performed on 25/27 (92.3%) culture positive specimens; 12/25 (48.0%) had "any resistance" detected and 3 (12.0%) were multi-drug resistant (MDR). Demographic and clinical features of drug resistant and drug susceptible TBM cases were similar. Beijing was the most common genotype (20/25; 80.0%) with 9/20 (45%) of the Beijing strains exhibiting drug resistance; including all 3 MDR strains. All (4/4) isoniazid resistant strains had mutations in the katG gene; 75% (3/4) of strains with phenotypic rifampicin resistance had mutations in the rpoB gene detected by Xpert MTB/RIF®. High rates of drug resistance were found among culture-confirmed TBM cases; most were Beijing strains.

SUBMITTER: Wang T

PROVIDER: S-EPMC4855176 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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High rate of drug resistance among tuberculous meningitis cases in Shaanxi province, China.

Wang Ting T Feng Guo-Dong GD Pang Yu Y Liu Jia-Yun JY Zhou Yang Y Yang Yi-Ning YN Dai Wen W Zhang Lin L Li Qiao Q Gao Yu Y Chen Ping P Zhan Li-Ping LP Marais Ben J BJ Zhao Yan-Lin YL Zhao Gang G

Scientific reports 20160504

The clinical and mycobacterial features of tuberculous meningitis (TBM) cases in China are not well described; especially in western provinces with poor tuberculosis control. We prospectively enrolled patients in whom TBM was considered in Shaanxi Province, northwestern China, over a 2-year period (September 2010 to December 2012). Cerebrospinal fluid specimens were cultured for Mycobacterium tuberculosis; with phenotypic and genotypic drug susceptibility testing (DST), as well as genotyping of ...[more]

PMID: 27143630

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Project description:Background: In Africa, tuberculosis is generally regarded as persisting as one of the most devastating infectious diseases. The pediatric population is particularly vulnerable, with infection of the brain in the form of tuberculous meningitis (TBM) being the most severe manifestation. TBM is often difficult to diagnose in its early stages because of its non-specific clinical presentation. Of particular concern is that late diagnosis, and subsequent delayed treatment, leads to high risk of long-term neurological sequelae, and even death. Using advanced technology and scientific expertise, we are intent on further describing the biochemistry behind this devastating neuroinflammatory disease, with the goal of improving upon its early diagnosis. Method: We used the highly sensitive analytical platform of gas chromatography-mass spectrometry (GC-MS) to analyze amino acid profiles of cerebrospinal fluid (CSF) collected from a cohort of 33 South African pediatric TBM cases, compared to 34 controls. Results: Through the use of a stringent quality assurance procedure and various statistical techniques, we were able to confidently identify five amino acids as being significantly elevated in TBM cases, namely, alanine, asparagine, glycine, lysine, and proline. We found also in an earlier untargeted metabolomics investigation that alanine can be attributed to increased CSF lactate levels, and lysine as a marker of lipid peroxidation. Alanine, like glycine, is an inhibitory neurotransmitter in the brain. Asparagine, as with proline, is linked to the glutamate-glutamine cycle. Asparagine is associated with the removal of increased nitrites in the brain, whereas elevated proline coincides with the classic biochemical marker of increased CSF protein in TBM. All five discriminatory amino acids are linked to ammonia due to increased nitrites in TBM. Conclusion: A large amount of untapped biochemical information is present in CSF of TBM cases, of which amino acid profiling through GC-MS has potential in aiding in earlier diagnosis, and hence crucial earlier treatment.

Dataset Information

High rate of drug resistance among tuberculous meningitis cases in Shaanxi province, China.

Publications

High rate of drug resistance among tuberculous meningitis cases in Shaanxi province, China.

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