The diagnosis and medical management of tuberculous meningitis in adults

Marais, Suzaan; Wilkinson, Robert J.

doi:10.7196/samj.9060

Cited by 6 publications

(7 citation statements)

References 15 publications

(23 reference statements)

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“…The diagnosis of TBM is particularly challenging in resourceconstrained areas owing to the expensive and invasive modalities required in making a proper diagnosis. These tests perform poorly individually (29,30), with a combination of several modalities including clinical presentation, CSF findings, neuroimaging, evidence of extraneural TB, and where possible, mycobacteriological confirmation, required for diagnosis (34). Access to these tests requires admission to a tertiary hospital in relatively well-resourced environments.…”

Section: Discussionmentioning

confidence: 99%

Potential of host serum protein biosignatures in the diagnosis of tuberculous meningitis in children

Manyelo

Solomons

Snyders

et al. 2019

Preprint

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Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis and results in high morbidity and mortality in children. Diagnostic delay contributes to the poor outcome. There is an urgent need for new tools for the rapid diagnosis of TBM, especially in children. Methods:We collected serum samples from children in whom TBM was suspected at a tertiary hospital in Cape Town, South Africa. Children were subsequently classified as having TBM or no TBM using a published uniform research case-definition. Using a multiplex cytokine array platform, we investigated the concentrations of serum biomarkers comprising 7-markers that were previously found to be of value in the diagnosis of adult pulmonary TB (CRP, SAA, CFH, IFN-γ, IP-10, Apo-AI and transthyretin) plus other potentially useful host biomarkers as diagnostic candidates for TBM. Findings:Of 47 children included in the study, 23 (48.9%) had a final diagnosis of TBM of which six had HIV co-infection. A modified version of the adult 7-marker biosignature in which transthyretin was replaced by NCAM1, diagnosed TBM in children with AUC of 0.80 (95% CI, 0.67-0.92), sensitivity of 73.9% (95% CI, 51.6-89.8%) and specificity of 66.7% (95% CI, 44.7-84.4%). A new childhood TBM specific 3-marker biosignature (adipsin, Aβ42 and IL-10) showed potential in the diagnosis of TBM, with AUC of 0.84 (95% CI, 0.73-0.96), sensitivity of 82.6% (95 CI, 61.2-95.0%) and specificity of 75.0% (95% CI, 53.3-90.2%) after leave-one-out cross validation.Conclusion: An adult 7-marker serum protein biosignature showed potential in the diagnosis of TBM in children. However, a smaller childhood TBM-specific biosignature demonstrated improved performance characteristics. Our data indicates that bloodbased biomarkers may be useful in the diagnosis of childhood TBM and require further investigation.

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Section: Discussionmentioning

confidence: 99%

Potential of host serum protein biosignatures in the diagnosis of tuberculous meningitis in children

Manyelo

Solomons

Snyders

et al. 2019

Preprint

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“…4 Selain itu, kultur bakteri juga kurang sensitif dan membutuhkan waktu sekurang-kurangnya dua minggu untuk dapat memberikan hasil. 6 Saat ini telah dikembangkan berbagai metode untuk melakukan diagnosis TB, mulai dari modifikasi kultur bakteri (MGIT, MODS), modifikasi pewarnaan (modified Ziehl-Neelsen, Auramine) hingga pemeriksaan berbasis amplifikasi DNA menggunakan metode polymerase chain reaction (PCR) seperti metode Xpert MTB/RIF (GeneXpert). 6 Kultur mycobacterial observation drug susceptibility (MODS) adalah modifikasi medium cair yang menggabungkan teknik identifikasi bakteri M. tuberculosis dengan drug susceptibility testing (DST).…”

Section: Pendahuluanunclassified

“…6 Saat ini telah dikembangkan berbagai metode untuk melakukan diagnosis TB, mulai dari modifikasi kultur bakteri (MGIT, MODS), modifikasi pewarnaan (modified Ziehl-Neelsen, Auramine) hingga pemeriksaan berbasis amplifikasi DNA menggunakan metode polymerase chain reaction (PCR) seperti metode Xpert MTB/RIF (GeneXpert). 6 Kultur mycobacterial observation drug susceptibility (MODS) adalah modifikasi medium cair yang menggabungkan teknik identifikasi bakteri M. tuberculosis dengan drug susceptibility testing (DST). 7,8 MODS memiliki sensitivitas lebih tinggi dibanding dengan medium solid, mencapai 65% dengan spesifisitas 98-100% dan membutuhkan waktu yang cenderung lebih singkat sekitar 6 hari hingga 4 minggu untuk memberikan hasil.…”

Section: Pendahuluanunclassified

“…[7][8][9] Pemeriksaan GeneXpert merupakan sebuah metode real-time PCR yang dapat mendeteksi M. tuberculosis sekaligus melakukan tes resistensi rifampisin (RIF). 6 GeneXpert memiliki beberapa kelebihan dibanding dengan PCR konvensional, yaitu dapat digunakan di luar lingkungan laboratorium karena menggunakan sistem closed-cartridge based dan tidak harus dilakukan oleh pengguna yang memiliki keahlian khusus. 9 Sejak bulan Desember tahun 2010, WHO merekomendasikan penggunaan GeneXpert sebagai alat diagnosis awal pada pasien MDR-TB dan pasien TB yang mengidap penyakit HIV.…”

Section: Pendahuluanunclassified

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Perbandingan Positivitas Metode MODS, Pewarnaan ZN, dan GeneXpert untuk Mendeteksi M. tuberculosis pada Pasien Meningitis TB

Paramitha

Sribudiani

Rizal³

2018

mkb

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Salah satu permasalahan dalam diagnosis meningitis tuberkulosis (TB) adalah rendahnya positivitas metode yang digunakan. Berbagai metode telah dikembangkan, mulai dari metode kultur MODS (microscopic observation drug susceptibility), pewarnaan Ziehl-Neelsen (ZN), hingga GeneXpert. Penelitian ini dilakukan untuk menentukan metode diagnostik terbaik mendeteksi M. tuberculosis berdasar atas nilai positivitasnya. Penelitian ini merupakan observasional analitik dengan rancangan potong lintang. Data berasal dari penelitian kohort dan ReDEFINe meningitis TB di Rumah Sakit Umum Pusat Dr. Hasan Sadikin Bandung. Data diambil dari case report form pasien dengan diagnosis meningitis TB pada periode Juli 2014-Juni 2016. Kriteria inklusi penelitian ini adalah usia ≥18 tahun dan memiliki hasil pemeriksaan MODS, pewarnaan ZN, dan GeneXpert. Analisis data menggunakan Uji Cochran's Q dan uji lanjut dengan Uji McNemar. Sebanyak 135 subjek penelitian memenuhi kriteria inklusi dan didapatkan positivitas deteksi M. tuberculosis menggunakan MODS, pewarnaan ZN, dan GeneXpert berturutturut adalah 46,7%; 20,0%; dan 37,8%. Nilai positivitas antara ketiga metode tersebut secara statistik berbeda bermakna dengan nilai p<0,05. Sensitivitas dan spesifisitas GeneXpert dibanding dengan MODS berturut-turut mencapai 68,3% dan 88,9%, sedangkan sensitivitas pewarnaan ZN sebesar 34,9% dan spesifisitas 93.1%. Berdasar atas nilai positivitas dan sensitivitas, hasil penelitian ini menunjukkan bahwa metode MODS masih merupakan metode diagnostik terbaik untuk meningitis TB.

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“…However, the use of the GeneXpert Ultra resulted in an improved negative predictive value in a more recent study on HIV-positive adults [9]. The diagnosis of TBM is mostly based on a combination of clinical findings, multiple laboratory tests on the CSF, imaging findings, and the exclusion of common differential diagnoses in routine clinical practice [10]. Diagnosing the disease in most high-burden, but resource-constrained settings is difficult due to the unavailability of most of these techniques, with children seen at primary and secondary healthcare facilities often having multiple missed opportunities; up to six visits before the eventual diagnosis of TBM are made [11].…”

Section: Introductionmentioning

confidence: 99%

Application of Cerebrospinal Fluid Host Protein Biosignatures in the Diagnosis of Tuberculous Meningitis in Children from a High Burden Setting

Manyelo

Solomons

Snyders

et al. 2019

Mediators of Inflammation

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Background. The diagnosis of tuberculous meningitis (TBM) especially in children is challenging. New tests are urgently needed for the diagnosis of the disease, especially in resource-limited settings. Methods. We collected cerebrospinal fluid (CSF) samples from children presenting with symptoms requiring investigation for meningitis at a tertiary hospital in Cape Town, South Africa. Children were later classified as TBM or no TBM using published case definitions. Using a multiplex platform, we investigated the concentrations of biomarkers comprising a previously established 3-marker biosignature (VEGF, IL-13, and LL-37) and other potentially useful host biomarkers as diagnostic candidates for TBM. Findings. Out of 47 children, age, 3 months to 13 years, 23 were diagnosed with TBM and six (16%) were HIV-infected. We validated the previously identified CSF biosignature (sensitivity of 95.7% (95% CI, 79.0-99.2%) and specificity of 37.5% (95% CI, 21.2-57.3%)). However, substitution of IL-13 and LL-37 with IFN-γ and MPO, respectively, resulted in improved accuracy (area under the ROC curve AUC=0.97, 95% CI, 0.92-1.00, up to 91.3% (21/23) sensitivity and up to 100% (24/24) specificity). An alternative four-marker biosignature (sICAM-1, MPO, CXCL8, and IFN-γ) also showed potential, with an AUC of 0.97. Conclusion. We validated a previously identified CSF biosignature and showed that refinement of this biosignature by incorporation of other biomarkers diagnosed TBM with high accuracy. Incorporation of these biomarkers into a point-of-care or bedside diagnostic test platform may result in the improved management of TBM in children.

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The diagnosis and medical management of tuberculous meningitis in adults

Cited by 6 publications

References 15 publications

Potential of host serum protein biosignatures in the diagnosis of tuberculous meningitis in children

Potential of host serum protein biosignatures in the diagnosis of tuberculous meningitis in children

Perbandingan Positivitas Metode MODS, Pewarnaan ZN, dan GeneXpert untuk Mendeteksi M. tuberculosis pada Pasien Meningitis TB

Application of Cerebrospinal Fluid Host Protein Biosignatures in the Diagnosis of Tuberculous Meningitis in Children from a High Burden Setting

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