Cerebrospinal T-Cell Responses Aid in the Diagnosis of Tuberculous Meningitis in a Human Immunodeficiency Virus– and Tuberculosis-Endemic Population

Patel, Vinod; Singh, Ravesh; Connolly, Cathy; Coovadia, Yacoob; Peer, Abdool K. C.; Parag, Priyashini; Kasprowicz, Victoria; Zumla, Alimuddin; Ndung’u, Thumbi; Dheda, Keertan

doi:10.1164/rccm.200912-1931oc

Cited by 66 publications

(82 citation statements)

References 46 publications

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“…A previous study showed that the sensitivity of T-SPOT.TB for TBM patients using a cut-off of 20 SFC per million mononuclear cells was 89z, which was lower than that for active pulmonary tuberculosis patients (16). In the present study, a total of 87 patients from both groups were subjected to the T-SPOT.TB test; the sensitivity and specificity of the test in the diagnosis of TBM were found to be 85.5z and 93.8z, respectively, suggesting an excellent diagnosing potential.…”

Section: Discussionmentioning

confidence: 90%

Validation of Thwaites' Diagnostic Scoring System for the Differential Diagnosis of Tuberculous Meningitis and Bacterial Meningitis

et al. 2014

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SUMMARY:To compare the clinical features of patients with tuberculous meningitis (TBM) and bacterial meningitis (BM) and to validate Thwaites' diagnostic scoring system for the differential diagnosis of TBM and BM, a retrospective review of 211 patients with TBM or BM who were admitted to Huashan Hospital, Fudan University, from 2007 to 2012 was conducted. The clinical characteristics and laboratory data were compared, and Thwaites' diagnostic scores were assessed at the time of admission for the differential diagnosis of TBM and BM. Significant differences were observed between the 2 groups in general information, clinical features, and cerebrospinal fluid characteristics. The sensitivity and specificity of Thwaites' diagnostic scoring system for the differential diagnosis of TBM and BM were found to be 98.2z and 43.6z, respectively, with positive and negative predictive values being 65.9z and 95.8z, respectively. The sensitivity and specificity for the differential diagnosis of TBM and initially treated BM were 98.2z and 82.9z, respectively, but were only 98.2z and 24.2z for that of TBM and partially treated BM, respectively. Thus, Thwaites' diagnostic scoring system was found to be highly effective for the differential diagnosis of TBM and initially treated BM but was found to be less effective for that of TBM and partially treated BM.

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Section: Discussionmentioning

confidence: 90%

Validation of Thwaites' Diagnostic Scoring System for the Differential Diagnosis of Tuberculous Meningitis and Bacterial Meningitis

et al. 2014

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“…We analyzed samples at a single time point within 12 months postinfection and defined this as primary infection. We also analyzed matched PBMC and cerebrospinal fluid (CSF) samples from a separate cohort of individuals presenting with chronic meningitis, as described previously (27). Briefly, 150 consecutive patients with suspected tuberculous meningitis (TBM) were prospectively recruited between January 2008 and April 2009 at the Inkosi Albert Luthuli Central Hospital (IALCH) in Durban, South Africa.…”

Section: Methodsmentioning

confidence: 99%

TRIM5α and TRIM22 Are Differentially Regulated According to HIV-1 Infection Phase and Compartment

Singh

Patel

Mureithi

et al. 2014

J Virol

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The antiviral role of TRIM E3 ligases in vivo is not fully understood. To test the hypothesis that TRIM5␣ and TRIM22 have differential transcriptional regulation and distinct anti-HIV roles according to infection phase and compartment, we measured TRIM5␣, TRIM22, and type I interferon (IFN-I)-inducible myxovirus resistance protein A (MxA) levels in peripheral blood mononuclear cells (PBMCs) during primary and chronic HIV-1 infection, with chronic infection samples being matched PBMCs and central nervous system (CNS)-derived cells. Associations with biomarkers of disease progression were explored. The impact of IFN-I, select proinflammatory cytokines, and HIV on TRIM E3 ligase-specific expression was investigated. PBMCs from individuals with primary and chronic HIV-1 infection had significantly higher levels of MxA and TRIM22 than did PBMCs from HIV-1-negative individuals (P < 0.05 for all comparisons). PBMCs from chronic infection had lower levels of TRIM5␣ than did PBMCs from primary infection or HIV-1-uninfected PBMCs (P ‫؍‬ 0.0001 for both). In matched CNS-derived samples and PBMCs, higher levels of MxA (P ‫؍‬ 0.001) and TRIM5␣ (P ‫؍‬ 0.0001) in the CNS were noted. There was a negative correlation between TRIM22 levels in PBMCs and plasma viral load (r ‫؍‬ ؊0.40; P ‫؍‬ 0.04). In vitro, IFN-I and, rarely, proinflammatory cytokines induced TRIM5␣ and TRIM22 in a cell type-dependent manner, and the knockdown of either protein in CD4 ؉ lymphocytes resulted in increased HIV-1 infection. These data suggest that there are infection-phase-specific and anatomically compartmentalized differences in TRIM5␣ and TRIM22 regulation involving primarily IFN-I and specific cell types and indicate subtle differences in the antiviral roles and transcriptional regulation of TRIM E3 ligases in vivo. IMPORTANCEType I interferon-inducible TRIM E3 ligases are a family of intracellular proteins with potent antiviral activities mediated through diverse mechanisms. However, little is known about the contribution of these proteins to antiviral immunity in vivo and how their expression is regulated. We show here that TRIM5␣ and TRIM22, two prominent members of the family, have different expression patterns in vivo and that the expression pattern depends on HIV-1 infection status and phase. Furthermore, expression differs in peripheral blood versus central nervous system anatomical sites of infection. Only TRIM22 expression correlated negatively with HIV-1 viral load, but gene silencing of both proteins enhances HIV-1 infection of target cells. We report subtle differences in TRIM5␣ and TRIM22 gene induction by IFN-I and proinflammatory cytokines in CD4 ؉ lymphocytes, monocytes, and neuronal cells. This study enhances our understanding of antiviral immunity by intrinsic antiviral factors and how their expression is determined.

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“…However, the current and previous studies showed that the sensitivity and specificity of CSF-MC ELISPOT with the manufacturer's recommend cut-off value (o6 spots per 2.5610 5 cells or o24 spots per 10 6 cells) were not high enough to use as a rapid rule-out or rulein test for diagnosing TBM (table s3). PATEL et al [2] reported that the CSF-MC ELISPOT assay, using a higher cut-off value rather than manufacturer's recommended cut-off value, especially in conjunction with other rapid tests, was an accurate rapid rule-in test for TBM in a tuberculosis-and HIV-endemic setting [2]. We found that CSF-MC/PBMC ELISPOT ratio o1.0, as well as CSF-MC ELISPOT assay with high cut-off value (o91 spots) was a useful rule-in test in an indeterminate tuberculosis-/low HIVburden setting.…”

mentioning

confidence: 99%

T-cell-based assays on cerebrospinal fluid and PBMCs for rapid diagnosis of TB meningitis in non-HIV patients

Kh¹,

Oh²,

Lee³

et al. 2012

European Respiratory Journal

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Cerebrospinal T-Cell Responses Aid in the Diagnosis of Tuberculous Meningitis in a Human Immunodeficiency Virus– and Tuberculosis-Endemic Population

Cited by 66 publications

References 46 publications

Validation of Thwaites' Diagnostic Scoring System for the Differential Diagnosis of Tuberculous Meningitis and Bacterial Meningitis

Validation of Thwaites' Diagnostic Scoring System for the Differential Diagnosis of Tuberculous Meningitis and Bacterial Meningitis

TRIM5α and TRIM22 Are Differentially Regulated According to HIV-1 Infection Phase and Compartment

T-cell-based assays on cerebrospinal fluid and PBMCs for rapid diagnosis of TB meningitis in non-HIV patients

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