scholarly journals Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics

2021 ◽  
Vol 4 ◽  
pp. 164
Author(s):  
Fiona V Cresswell ◽  
Angharad G. Davis ◽  
Kusum Sharma ◽  
Robindra Basu Roy ◽  
Ahmad Rizal Ganiem ◽  
...  

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.

2020 ◽  
Vol 4 ◽  
pp. 164
Author(s):  
Fiona V Cresswell ◽  
Angharad G. Davis ◽  
Kusum Sharma ◽  
Robindra Basu Roy ◽  
Ahmad Rizal Ganiem ◽  
...  

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.


2019 ◽  
Vol 4 ◽  
pp. 164
Author(s):  
Fiona V Cresswell ◽  
Angharad G. Davis ◽  
Kusum Sharma ◽  
Robindra Basu Roy ◽  
Ahmad Rizal Ganiem ◽  
...  

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.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fan Jin ◽  
Jing Xie ◽  
Huan-ling Wang

Abstract Objectives We analysed the peripheral blood lymphocyte subsets of human immunodeficiency virus (HIV)-negative patients infected with pneumocystis pneumonia (PCP) to determine the relationships between the levels of different types of lymphocytes and the prognosis of patients. Methods We retrospectively reviewed HIV-negative patients with PCP diagnosed in our department. All the eligible patients underwent lymphocyte subset analysis on admission. Results A total of 88 HIV-negative PCP patients were enrolled in the study. In univariate analyses, low CD4+ T cell count, low CD8+ T cell count, and low natural killer cell (NK cell) count were associated with higher in-hospital mortality. CD8+ T cell count ≤300/μL was found to be an independent risk factor for poor prognosis in multivariate logistical regression analysis (p = 0.015, OR = 11.526, 95% CI = 1.597–83.158). Although low CD4+ T cell and NK cell counts were not independent risk factors, the mortality rates of PCP patients decreased as the CD4+ T cell and NK cell counts increased. Conclusion The immune process of Pneumocystis jirovecii infection is complex but important. We propose that lymphocyte subsets could give clinicians a better understanding of patient immune status, helping with the early identification of potentially lethal infections and treatment decision making, such as adjusting the immunosuppressive regimen and choosing an appropriate patient monitoring level.


2020 ◽  
Vol 61 (8) ◽  
pp. 1869-1876 ◽  
Author(s):  
Yan Gu ◽  
Yuanyuan Jin ◽  
Jie Ding ◽  
Wu Yujie ◽  
Qinglin Shi ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Cathy Nisha John ◽  
Lawrence Xavier Graham Stephen ◽  
Charlene Wilma Joyce Africa

Background. The “red complex” microorganisms, namely,Porphyromonas gingivalis,Treponema denticola, andTannerella forsythiaare considered as potential pathogens causing HIV-associated periodontal diseases. Moreover, it has been recognized that an association exists between CD4+ T cell counts and periodontal disease progression.Objective. To establish whether CD4+ T cell counts or oral hygiene plays a greater role in producing BANA-positive results in HIV-associated periodontal disease.Materials and Methods. One hundred and twenty HIV-positive patients participated in the study, and their CD4+ T cell counts were obtained from their medical records. The six Ramfjord teeth were used for evaluating periodontal clinical indices and subgingival plaque sampling. BANA test was used for the detection and prevalence of the “red complex” bacteria in plaque samples.Results. A majority of 69.17% HIV-positive patients were BANA-positive. No significant associations were found between BANA and CD4+ T cell counts. A highly significant association was found between BANA with probing depth and clinical attachment level (P≤0.0001) and between BANA and the use of interdental aids (P=0.0168).Conclusion. HIV-associated periodontal diseases are strongly related to oral hygiene practices rather than the effect of CD4+ T cell counts, and the use of interdental aids was marked as a significant predictor of BANA-negative plaque samples.


2012 ◽  
Vol 19 (10) ◽  
pp. 1693-1696 ◽  
Author(s):  
Veena V. Ramalingam ◽  
Monika Mani ◽  
Vijayanand C. Sundaresan ◽  
Ramesh J. Karunaiya ◽  
Jaiprasath Sachithanandham ◽  
...  

ABSTRACTCD4+T cell count estimations are subject to high variations; hence, in this study, the previous day's tested samples were included routinely as the internal quality controls. The percentages of variation of the 2-day values were analyzed for 280 observations and the mean variation for CD4+and CD3+T cell counts ranged from 5.21% to 9.66%. This method is a good internal quality control (IQC) procedure for the estimation of CD3+and CD4+T cell counts in resource-poor settings.


PEDIATRICS ◽  
1994 ◽  
Vol 94 (2) ◽  
pp. 276-276
Author(s):  
Joseph Church

HIV-infected children are at risk for developing disseminated MAC infection. Children older than 5 years and those with CD4+ T-cell counts &lt;100/mm3 (&lt;100 x 106/liter) are at greatest risk.


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