Pretreatment Cerebrospinal Fluid Bacterial Load Correlates With Inflammatory Response and Predicts Neurological Events During Tuberculous Meningitis Treatment

Thuong, Nguyen T T; Vinh, Dao Nguyen; Hoang, Hai; Thu, Do Dang Anh; Nhat, Le Thanh Hoang; Heemskerk, Dorothee; Bang, Nguyen Duc; Caws, Maxine; Nguyen, T H; Thwaites, Guy

doi:10.1093/infdis/jiy588

Cited by 33 publications

(32 citation statements)

References 25 publications

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“…The sensitivity of both assays was higher in HIVinfected than in HIV-uninfected individuals, probably reflecting the larger numbers of bacteria in CSF samples from these patients. 19 Additionally, Xpert Ultra appeared to be able to detect more patients with tuberculous meningitis with very low or trace levels of bacteria in their CSF and to be more sensitive than Xpert once antituberculosis treatment had been started. Previous studies have suggested that Xpert Ultra is significantly more sensitive than Xpert for the diagnosis of tuberculous meningitis.…”

Section: Discussionmentioning

confidence: 99%

Xpert MTB/RIF Ultra versus Xpert MTB/RIF for the diagnosis of tuberculous meningitis: a prospective, randomised, diagnostic accuracy study

Donovan

Thu

Phu

et al. 2020

The Lancet Infectious Diseases

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116

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Background Xpert MTB/RIF Ultra (Xpert Ultra) might have higher sensitivity than its predecessor, Xpert MTB/RIF (Xpert), but its role in tuberculous meningitis diagnosis is uncertain. We aimed to compare Xpert Ultra with Xpert for the diagnosis of tuberculous meningitis in HIV-uninfected and HIV-infected adults. Methods In this prospective, randomised, diagnostic accuracy study, adults (≥16 years) with suspected tuberculous meningitis from a single centre in Vietnam were randomly assigned to cerebrospinal fluid testing by either Xpert Ultra or Xpert at baseline and, if treated for tuberculous meningitis, after 3-4 weeks of treatment. Test performance (sensitivity, specificity, and positive and negative predictive values) was calculated for Xpert Ultra and Xpert and compared against clinical and mycobacterial culture reference standards. Analyses were done for all patients and by HIV status.

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Section: Discussionmentioning

confidence: 99%

Xpert MTB/RIF Ultra versus Xpert MTB/RIF for the diagnosis of tuberculous meningitis: a prospective, randomised, diagnostic accuracy study

Donovan

Thu

Phu

et al. 2020

The Lancet Infectious Diseases

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116

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“…Thuong et al . found that among 692 Vietnamese adults with TBM, pre-treatment CSF M.tb load (by Xpert Ct) was correlated with increased CSF neutrophil counts, increased cytokine production, and new neurological events after treatment initiation, but not death 43 .…”

Section: Tbm Pathogenesismentioning

confidence: 95%

“…TBM patients generally have low bacterial loads in CSF which causes difficulties in both diagnosis and ability to study bacterial load evolution-related pathophysiology. The time-to-positivity of a culture and cycle threshold (Ct) of nucleic acid amplification tests such as GeneXpert MTB/Rif (Xpert) can provide an indication of likely bacterial burden 43 . Over 50% of diagnosed cases are microbiologically undetectable and defined as ‘probable’ or ‘possible’ TBM which obviously limits this approach 44 .…”

Section: Tbm Pathogenesismentioning

confidence: 99%

“…This framework likely applies to TBM based on evidence of both failed immunity and excessive inflammation being linked to increased TBM pathology, see Figure 3 23 , 51 , 52 . Both the microbe and the host contribute to host damage and where an individual patient’s immune response lies on the continuum of the damage response framework parabola determines the nature of the disease process 16 , 43 , 53 . Evidence from recent studies shows LTA4H genotype, CSF cytokines and CSF immune cells such as neutrophils are determinants of inflammatory state, which impacts both bacterial growth and host damage and thus leads to different outcomes.…”

Section: Tbm Pathogenesismentioning

confidence: 99%

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Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics

et al. 2020

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The pathogenesis of Tuberculous meningitis (TBM) is poorly understood, but contemporary molecular biology technologies have allowed for recent improvements in our understanding of TBM. For instance, neutrophils appear to play a significant role in the immunopathogenesis of TBM, and either a paucity or an excess of inflammation can be detrimental in TBM. Further, severity of HIV-associated immunosuppression is an important determinant of inflammatory response; patients with the advanced immunosuppression (CD4+ T-cell count of <150 cells/μL) having higher CSF neutrophils, greater CSF cytokine concentrations and higher mortality than those with CD4+ T-cell counts > 150 cells/μL. Host genetics may also influence outcomes with LT4AH genotype predicting inflammatory phenotype, steroid responsiveness and survival in Vietnamese adults with TBM. Whist in Indonesia, CSF tryptophan level was a predictor of survival, suggesting tryptophan metabolism may be important in TBM pathogenesis. These varying responses mean that we must consider whether a “one-size-fits-all” approach to anti-bacillary or immunomodulatory treatment in TBM is truly the best way forward. Of course, to allow for proper treatment, early and rapid diagnosis of TBM must occur. Diagnosis has always been a challenge but the field of TB diagnosis is evolving, with sensitivities of at least 70% now possible in less than two hours with GeneXpert MTB/Rif Ultra. In addition, advanced molecular techniques such as CRISPR-MTB and metagenomic next generation sequencing may hold promise for TBM diagnosis. Host-based biomarkers and signatures are being further evaluated in childhood and adult TBM as adjunctive biomarkers as even with improved molecular assays, cases are still missed. A better grasp of host and pathogen behaviour may lead to improved diagnostics, targeted immunotherapy, and possibly biomarker-based, patient-specific treatment regimens.

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“…10 Hingga saat ini, masih belum ditemukan patofisiologi yang jelas mengenai perubahan spesifik dari tiap parameter LCS, seperti yang dilaporkan oleh Thuong. 13 Pemeriksaan LCS juga dipengaruhi oleh prosedur pengambilan sampel yang kurang tepat, kadar patogen itu sendiri, dan penggunaan antibiotik yang dapat mengakibatkan hasil pemeriksaan LCS mengalami perubahan atau tampak normal. 11 Berbagai jenis infeksi yang terjadi pada tubuh manusia dapat memicu timbulnya demam atau panas badan.…”

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Gambaran Cairan Serebrospinal pada Pasien Anak dengan Infeksi Susunan Saraf Pusat di Rumah Sakit Rujukan Jawa Barat

Prakoso

Dewi

Sugianli³

2020

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Latar belakang. Infeksi pada susunan saraf pusat (SSP) dapat memberikan dampak permanen, seperti ganguan fungsi kognitif dan fisik apabila terlambat mendapatkan penanganan. Perubahan komposisi cairan serebrospinalis (LCS) dapat digunakan sebagai indikator pada infeksi SSP. Studi kepustakaan pada karakteristik perubahan komposisi LCS masih sulit ditemukan sehingga diperlukan studi lebih lanjut mengenai hal ini.Tujuan. Mengetahui gambaran LCS pada pasien anak dengan infeksi susunan saraf pusat.Metode. Deskriptif potong lintang terhadap rekam medis pasien anak dengan infeksi susunan saraf pusat rawat inap di RSUP Dokter Hasan Sadikin Bandung periode Januari 2015-Agustus 2019.Hasil. Dari 211 subjek penelitian dengan rentang usia 1 bulan hingga 18 tahun diperoleh rerata usia 7,18, median usia 5, dan standar deviasi usia 6,53. Diperoleh pada kelompok usia 1 bulan-2 tahun 39,8%, 3-6 tahun 14,7%;, 7-12 tahun 12,8%; dan 13-18 tahun 32,7%. Diperoleh 45,5% sampel merupakan infeksi tuberkulosis (TB), 21,3% sampel infeksi virus, 9,5% sampel infeksi bakteri, dan 23,7% sampel infeksi tidak spesifik.Kesimpulan. Pemeriksaan LCS sangat penting dilakukan untuk menunjang diagnosis infeksi SSP. Sebagian besar LCS menunjukkan gambaran infeksi yang disebabkan oleh TB

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Pretreatment Cerebrospinal Fluid Bacterial Load Correlates With Inflammatory Response and Predicts Neurological Events During Tuberculous Meningitis Treatment

Cited by 33 publications

References 25 publications

Xpert MTB/RIF Ultra versus Xpert MTB/RIF for the diagnosis of tuberculous meningitis: a prospective, randomised, diagnostic accuracy study

Xpert MTB/RIF Ultra versus Xpert MTB/RIF for the diagnosis of tuberculous meningitis: a prospective, randomised, diagnostic accuracy study

Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics

Gambaran Cairan Serebrospinal pada Pasien Anak dengan Infeksi Susunan Saraf Pusat di Rumah Sakit Rujukan Jawa Barat

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