Central nervous system infection diagnosis by next-generation sequencing: a glimpse into the future?

Japanese encephalitis virus was detected by deep sequencing for the first time in urine of a 16-year-old boy with encephalitis. Seroconversion and polymerase chain reaction analysis confirmed the metagenomics finding. Urine is useful for diagnosis of flaviviral encephalitis, whereas deep sequencing can be a panpathogen assay for the diagnosis of life-threatening infectious diseases

The influence of Strongyloides stercoralis co-infection on the presentation, pathogenesis and outcome of tuberculous meningitis

Background Helminth infections may modulate the inflammatory response to Mycobacterium tuberculosis and influence disease presentation and outcome. Strongyloides stercoralis is common amongst populations with high tuberculosis prevalence. Our aim was to determine if S. stercoralis co-infection influenced clinical presentation, cerebrospinal fluid (CSF) inflammation, and outcome from tuberculous meningitis (TBM). Methods From June 2017 to December 2019, 668 Vietnamese adults with TBM, enrolled in the ACT HIV or LAST ACT trials (NCT03092817; NCT03100786), underwent pre-treatment S. stercoralis testing by serology, stool microscopy, and/or stool PCR. Comparisons of pre-treatment TBM severity, CSF inflammation (including cytokines), and 3-month clinical endpoints were performed in active S. stercoralis infected and uninfected groups. Results Overall, 9.4% (63/668) participants tested positive for S. stercoralis. Active S. stercoralis infection was significantly associated with reduced pre-treatment CSF neutrophils (3 cells/mm 3[0-25] vs. 14 (cells/mm 3[1-83], p=0.04), and with reduced CSF IFN-ɣ, IL-2, and TNF-α concentrations (11.4 vs. 56.0pg/mL p=0.01; 33.1 vs. 54.5pg/mL p=0.03; 4.5 vs. 11.9pg/mL p=0.02, respectively), compared with uninfected participants. Neurological complications by 3 months were significantly reduced in active S. stercoralis infection vs. uninfected participants (3.8%[1/26] vs. 30.0%[33/110], respectively, p=0.01). Conclusions S. stercoralis co-infection may modulate the intracerebral inflammatory response to M. tuberculosis and improve TBM clinical outcomes

Central nervous system infection diagnosis by next-generation sequencing: a glimpse into the future?

Japanese encephalitis virus was detected by deep sequencing for the first time in urine of a 16-year-old boy with encephalitis. Seroconversion and polymerase chain reaction analysis confirmed the metagenomics finding. Urine is useful for diagnosis of flaviviral encephalitis, whereas deep sequencing can be a panpathogen assay for the diagnosis of life-threatening infectious diseases

Cerebrospinal fluid MinION sequencing of 16S rRNA gene for rapid and accurate diagnosis of bacterial meningitis

Analysis of angiotensin-converting enzyme 2 (ACE2) from different species sheds some light on cross-species receptor usage of a novel coronavirus 2019-nCo

A randomised double blind placebo controlled phase 2 trial of adjunctive aspirin for tuberculous meningitis in HIV-uninfected adults

Background: Adjunctive dexamethasone reduces mortality from tuberculous meningitis (TBM) but not disability, which is associated with brain infarction. We hypothesised that aspirin prevents TBM-related brain infarction through its anti-thrombotic, anti-inflammatory, and pro-resolution properties. Methods: We conducted a randomised controlled trial in HIV-uninfected adults with TBM of daily aspirin 81mg or 1000mg, or placebo, added to the first 60 days of anti-tuberculosis drugs and dexamethasone (NCT02237365). The primary safety endpoint was gastro-intestinal or cerebral bleeding by 60 days; the primary efficacy endpoint was new brain infarction confirmed by magnetic resonance imaging or death by 60 days. Secondary endpoints included 8-month survival and neuro-disability; the number of grade 3&amp;4 and serious adverse events; and cerebrospinal fluid (CSF) inflammatory lipid mediator profiles. Findings: 41 participants were randomised to placebo, 39 to aspirin 81mg/day, and 40 to aspirin 1000mg/day between October 2014 and May 2016. TBM was proven microbiologically in 92/120(76.7%) and baseline brain imaging revealed ≥1 infarct in 40/114(35.1%) participants. The primary safety outcome occurred in 5/36(13.9%) given placebo, and in 8/35(22.9%) and 8/40(20.0%) given 81mg and 1000mg aspirin respectively (P=0.59). The primary efficacy outcome occurred in 11/38(28.9%) given placebo, 8/36(22.2%) given aspirin 81mg, and 6/38(15.8%) given 1000mg aspirin (P=0.40). Planned subgroup analysis showed a significant interaction between aspirin treatment effect and diagnostic category (Pheterogeneity=0.01) and suggested a potential reduction in new infarcts and deaths by day 60 in the aspirin treated participants with microbiologically confirmed TBM (11/32(34.4%) events in placebo vs. 4/27(14.8%) in aspirin 81 mg vs. 3/28 (10.7%) in aspirin 1000mg; P=0.06). CSF analysis demonstrated aspirin dose-dependent inhibition of thromboxane A2 and upregulation of pro-resolving CSF protectins. Interpretation: The addition of aspirin to dexamethasone may improve outcomes from TBM and warrants investigation in a large phase 3 trial.</p