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Hoang T Hai - One of the best experts on this subject based on the ideXlab platform.

  • comparison of the mycobacterium tuberculosis molecular Bacterial Load assay microscopy and genexpert versus liquid culture for viable Bacterial Load quantification before and after starting pulmonary tuberculosis treatment
    Tuberculosis, 2019
    Co-Authors: Hoang T Hai, Dao N Vinh, Do Dang Anh Thu, Nguyen T Hanh, Nguyen Hoan Phu, Vijay Srinivasan, Guy Thwaites, Nguyen Thuy Thuong Thuong
    Abstract:

    Abstract Molecular Bacterial Load assay (MBLA) rapidly quantifies viable Mycobacterium tuberculosis (Mtb) and may be useful for monitoring treatment response and treatment efficacy. We conducted a prospective study in 56 adults with pulmonary tuberculosis from whom 244 sputum samples were collected before and during the first month of treatment. We evaluated MBLA for early monitoring of Bacterial burden and investigated bactericidal activities of first-line therapy in patients infected with drug susceptible and resistant isolates. Mtb Loads measured by MBLA and culture were correlated after one-week (r = 0.56) and one-month (r = 0.73) of treatment. Correlations between culture and GeneXpert or microscopy were weaker during treatment. Mtb Load by MBLA declined more rapidly than GeneXpert after one-week (2.73 Ct, P  MBLA performed better than GeneXpert and microscopy in comparison to culture for quantifying viable Mtb during treatment. It can be used for monitoring Bacterial Load during TB treatment, facilitating early detection of treatment failure thus improving outcomes.

  • pretreatment cerebrospinal fluid Bacterial Load correlates with inflammatory response and predicts neurological events during tuberculous meningitis treatment
    The Journal of Infectious Diseases, 2019
    Co-Authors: N T Thuong, Hoang T Hai, Dao N Vinh, Do Dang Anh Thu, Le Thanh Hoang Nhat, Dorothee Heemskerk, Nguyen Duc Bang, Maxine Caws, Nguyen Thi Hoang Mai
    Abstract:

    Background Mycobacterium tuberculosis (Mtb) bacillary Load in the brain of those with tuberculous meningitis (TBM) may reflect the host ability to control the pathogen and determine disease severity and treatment outcomes. Methods We measured pre-treatment cerebrospinal fluid (CSF) Mtb Bacterial Load by GeneXpert in 692 adults with TBM. We sought to understand the relationship between CSF Bacterial Load and inflammation, and their respective impact on disease severity and treatment outcomes. Results Ten-fold higher Mtb Load was associated with increased disease severity (Odds Ratio=1.59, p=0.001 for grade 1 versus grade 3), and increased CSF neutrophils (r=0.364, p<0.0001) and cytokine concentrations (r=0.438, p<0.0001). High Mtb Load predicted new neurological events after starting treatment (Multinomial logistic regression, p=0.005), but not death. Death was previously associated with attenuated inflammatory response at the start of treatment, with reduced cytokine concentrations compared to survivors. In contrast, patients with high pre-treatment CSF Bacterial Loads, cytokines, and neutrophils were more likely to subsequently suffer neurological events. Conclusions Pre-treatment GeneXpert-derived Mtb Load may be a useful predictor of neurological complications occurring during TBM treatment. Therapeutic strategies aimed at reducing neurological complications and deaths from TBM may need reassessment, given the evidence for their divergent pathogenesis.

  • pretreatment cerebrospinal fluid Bacterial Load correlates with inflammatory response and predicts neurological events during tuberculous meningitis treatment
    The Journal of Infectious Diseases, 2019
    Co-Authors: Nguyen Thuy Thuong Thuong, Hoang T Hai, Dao N Vinh, Do Dang Anh Thu, Le Thanh Hoang Nhat, Dorothee Heemskerk, Nguyen Duc Bang, Maxine Caws, Nguyen Thi Hoang Mai
    Abstract:

    BACKGROUND The Mycobacterium tuberculosis Load in the brain of individuals with tuberculous meningitis (TBM) may reflect the host's ability to control the pathogen, determine disease severity, and determine treatment outcomes. METHODS We used the GeneXpert assay to measure the pretreatment M. tuberculosis Load in cerebrospinal fluid (CSF) specimens from 692 adults with TBM. We sought to understand the relationship between CSF Bacterial Load and inflammation, and their respective impact on disease severity and treatment outcomes. RESULTS A 10-fold higher M. tuberculosis Load was associated with increased disease severity (odds ratio, 1.59; P = .001 for the comparison between grade 1 and grade 3 severity), CSF neutrophil count (r = 0.364 and P < .0001), and cytokine concentrations (r = 0.438 and P < .0001). A high M. tuberculosis Load predicted new neurological events after starting treatment (P = .005, by multinomial logistic regression) but not death. Patients who died had an attenuated inflammatory response at the start of treatment, with reduced cytokine concentrations as compared to survivors. In contrast, patients with high pretreatment CSF Bacterial Loads, cytokine concentrations, and neutrophil counts were more likely to subsequently experience neurological events. CONCLUSIONS The pretreatment GeneXpert-determined M. tuberculosis Load may be a useful predictor of neurological complications occurring during TBM treatment. Given the evidence for the divergent pathogenesis of TBM-associated neurological complications and deaths, therapeutic strategies to reduce them may need reassessment.

  • virulence of mycobacterium tuberculosis clinical isolates is associated with sputum pre treatment Bacterial Load lineage survival in macrophages and cytokine response
    Frontiers in Cellular and Infection Microbiology, 2018
    Co-Authors: Tram Ttb, Hoang T Hai, Hoang Ngoc Nhung, Srinivasan Vijay, Thu Dda, Ha Vtn, Tran D Dinh, Philip M Ashton, Nguyen Thi Hanh, Nguyen Hoan Phu
    Abstract:

    It is uncertain whether differences in Mycobacterium tuberculosis (Mtb) virulence defined in vitro influence clinical tuberculosis pathogenesis, transmission, and mortality. We primarily used a macrophage lysis model to characterize the virulence of Mtb isolates collected from 153 Vietnamese adults with pulmonary tuberculosis. The virulence phenotypes were then investigated for their relationship with sputum Bacterial Load, Bacterial lineages, Bacterial growth and cytokine responses in macrophages. Over 6 days of infection, 34 isolates (22.2%) showed low virulence (< 5% macrophages lysed), 46 isolates (30.1%) showed high virulence (≥ 90% lysis of macrophages), and 73 isolates (47.7%) were of intermediate virulence (5-90% macrophages lysed). Highly virulent isolates were associated with an increased Bacterial Load in patients’ sputum before anti-tuberculosis therapy (P= 0.02). Isolate-dependent virulence phenotype was consistent in both THP-1 and human monocyte-derived macrophages. High virulence isolates survived better and replicated in macrophages one hundred fold faster than those with low virulence. Macrophages infected with high virulence isolates produced lower concentrations of TNF-α and IL-6 (P= 0.002 and 0.0005, respectively), but higher concentration of IL-1β (P= 5.1×10-5) compared to those infected with low virulence isolates. High virulence was strongly associated with East Asian/Beijing lineage [P= 0.002, Odd ratio (OR)= 4.32, 95% confident intervals (CI) 1.68 – 11.13]. The association between virulence phenotypes, Bacterial growth, and proinflammatory cytokines in macrophages suggest the suppression of certain proinflammatory cytokines (TNF-α and IL-6) but not IL-1β allows better intracellular survival of highly virulent Mtb. This could result in rapid macrophage lysis and higher Bacterial Load in sputum of patients infected with high virulence isolates, which may contribute to the pathogenesis and success of the Beijing lineage.

Nguyen Thi Hoang Mai - One of the best experts on this subject based on the ideXlab platform.

  • pretreatment cerebrospinal fluid Bacterial Load correlates with inflammatory response and predicts neurological events during tuberculous meningitis treatment
    The Journal of Infectious Diseases, 2019
    Co-Authors: N T Thuong, Hoang T Hai, Dao N Vinh, Do Dang Anh Thu, Le Thanh Hoang Nhat, Dorothee Heemskerk, Nguyen Duc Bang, Maxine Caws, Nguyen Thi Hoang Mai
    Abstract:

    Background Mycobacterium tuberculosis (Mtb) bacillary Load in the brain of those with tuberculous meningitis (TBM) may reflect the host ability to control the pathogen and determine disease severity and treatment outcomes. Methods We measured pre-treatment cerebrospinal fluid (CSF) Mtb Bacterial Load by GeneXpert in 692 adults with TBM. We sought to understand the relationship between CSF Bacterial Load and inflammation, and their respective impact on disease severity and treatment outcomes. Results Ten-fold higher Mtb Load was associated with increased disease severity (Odds Ratio=1.59, p=0.001 for grade 1 versus grade 3), and increased CSF neutrophils (r=0.364, p<0.0001) and cytokine concentrations (r=0.438, p<0.0001). High Mtb Load predicted new neurological events after starting treatment (Multinomial logistic regression, p=0.005), but not death. Death was previously associated with attenuated inflammatory response at the start of treatment, with reduced cytokine concentrations compared to survivors. In contrast, patients with high pre-treatment CSF Bacterial Loads, cytokines, and neutrophils were more likely to subsequently suffer neurological events. Conclusions Pre-treatment GeneXpert-derived Mtb Load may be a useful predictor of neurological complications occurring during TBM treatment. Therapeutic strategies aimed at reducing neurological complications and deaths from TBM may need reassessment, given the evidence for their divergent pathogenesis.

  • pretreatment cerebrospinal fluid Bacterial Load correlates with inflammatory response and predicts neurological events during tuberculous meningitis treatment
    The Journal of Infectious Diseases, 2019
    Co-Authors: Nguyen Thuy Thuong Thuong, Hoang T Hai, Dao N Vinh, Do Dang Anh Thu, Le Thanh Hoang Nhat, Dorothee Heemskerk, Nguyen Duc Bang, Maxine Caws, Nguyen Thi Hoang Mai
    Abstract:

    BACKGROUND The Mycobacterium tuberculosis Load in the brain of individuals with tuberculous meningitis (TBM) may reflect the host's ability to control the pathogen, determine disease severity, and determine treatment outcomes. METHODS We used the GeneXpert assay to measure the pretreatment M. tuberculosis Load in cerebrospinal fluid (CSF) specimens from 692 adults with TBM. We sought to understand the relationship between CSF Bacterial Load and inflammation, and their respective impact on disease severity and treatment outcomes. RESULTS A 10-fold higher M. tuberculosis Load was associated with increased disease severity (odds ratio, 1.59; P = .001 for the comparison between grade 1 and grade 3 severity), CSF neutrophil count (r = 0.364 and P < .0001), and cytokine concentrations (r = 0.438 and P < .0001). A high M. tuberculosis Load predicted new neurological events after starting treatment (P = .005, by multinomial logistic regression) but not death. Patients who died had an attenuated inflammatory response at the start of treatment, with reduced cytokine concentrations as compared to survivors. In contrast, patients with high pretreatment CSF Bacterial Loads, cytokine concentrations, and neutrophil counts were more likely to subsequently experience neurological events. CONCLUSIONS The pretreatment GeneXpert-determined M. tuberculosis Load may be a useful predictor of neurological complications occurring during TBM treatment. Given the evidence for the divergent pathogenesis of TBM-associated neurological complications and deaths, therapeutic strategies to reduce them may need reassessment.

Maxine Caws - One of the best experts on this subject based on the ideXlab platform.

  • pretreatment cerebrospinal fluid Bacterial Load correlates with inflammatory response and predicts neurological events during tuberculous meningitis treatment
    The Journal of Infectious Diseases, 2019
    Co-Authors: N T Thuong, Hoang T Hai, Dao N Vinh, Do Dang Anh Thu, Le Thanh Hoang Nhat, Dorothee Heemskerk, Nguyen Duc Bang, Maxine Caws, Nguyen Thi Hoang Mai
    Abstract:

    Background Mycobacterium tuberculosis (Mtb) bacillary Load in the brain of those with tuberculous meningitis (TBM) may reflect the host ability to control the pathogen and determine disease severity and treatment outcomes. Methods We measured pre-treatment cerebrospinal fluid (CSF) Mtb Bacterial Load by GeneXpert in 692 adults with TBM. We sought to understand the relationship between CSF Bacterial Load and inflammation, and their respective impact on disease severity and treatment outcomes. Results Ten-fold higher Mtb Load was associated with increased disease severity (Odds Ratio=1.59, p=0.001 for grade 1 versus grade 3), and increased CSF neutrophils (r=0.364, p<0.0001) and cytokine concentrations (r=0.438, p<0.0001). High Mtb Load predicted new neurological events after starting treatment (Multinomial logistic regression, p=0.005), but not death. Death was previously associated with attenuated inflammatory response at the start of treatment, with reduced cytokine concentrations compared to survivors. In contrast, patients with high pre-treatment CSF Bacterial Loads, cytokines, and neutrophils were more likely to subsequently suffer neurological events. Conclusions Pre-treatment GeneXpert-derived Mtb Load may be a useful predictor of neurological complications occurring during TBM treatment. Therapeutic strategies aimed at reducing neurological complications and deaths from TBM may need reassessment, given the evidence for their divergent pathogenesis.

  • pretreatment cerebrospinal fluid Bacterial Load correlates with inflammatory response and predicts neurological events during tuberculous meningitis treatment
    The Journal of Infectious Diseases, 2019
    Co-Authors: Nguyen Thuy Thuong Thuong, Hoang T Hai, Dao N Vinh, Do Dang Anh Thu, Le Thanh Hoang Nhat, Dorothee Heemskerk, Nguyen Duc Bang, Maxine Caws, Nguyen Thi Hoang Mai
    Abstract:

    BACKGROUND The Mycobacterium tuberculosis Load in the brain of individuals with tuberculous meningitis (TBM) may reflect the host's ability to control the pathogen, determine disease severity, and determine treatment outcomes. METHODS We used the GeneXpert assay to measure the pretreatment M. tuberculosis Load in cerebrospinal fluid (CSF) specimens from 692 adults with TBM. We sought to understand the relationship between CSF Bacterial Load and inflammation, and their respective impact on disease severity and treatment outcomes. RESULTS A 10-fold higher M. tuberculosis Load was associated with increased disease severity (odds ratio, 1.59; P = .001 for the comparison between grade 1 and grade 3 severity), CSF neutrophil count (r = 0.364 and P < .0001), and cytokine concentrations (r = 0.438 and P < .0001). A high M. tuberculosis Load predicted new neurological events after starting treatment (P = .005, by multinomial logistic regression) but not death. Patients who died had an attenuated inflammatory response at the start of treatment, with reduced cytokine concentrations as compared to survivors. In contrast, patients with high pretreatment CSF Bacterial Loads, cytokine concentrations, and neutrophil counts were more likely to subsequently experience neurological events. CONCLUSIONS The pretreatment GeneXpert-determined M. tuberculosis Load may be a useful predictor of neurological complications occurring during TBM treatment. Given the evidence for the divergent pathogenesis of TBM-associated neurological complications and deaths, therapeutic strategies to reduce them may need reassessment.

Joshua T Schiffer - One of the best experts on this subject based on the ideXlab platform.

  • complementing 16s rrna gene amplicon sequencing with total Bacterial Load to infer absolute species concentrations in the vaginal microbiome
    mSystems, 2020
    Co-Authors: Florencia Tettamanti A Boshier, Sujatha Srinivasan, Anthony Lopez, Noah G Hoffman, Sean Proll, David N Fredricks, Joshua T Schiffer
    Abstract:

    ABSTRACT Whereas 16S rRNA gene amplicon sequencing quantifies relative abundances of Bacterial taxa, variation in total Bacterial Load between samples restricts its ability to reflect absolute concentrations of individual Bacterial species. Quantitative PCR (qPCR) can quantify individual species, but it is not practical to develop a suite of qPCR assays for every bacterium present in a diverse sample. We sought to determine the accuracy of an inferred measure of Bacterial concentration using total Bacterial Load and relative abundance. We analyzed 1,320 samples from 20 women with a history of frequent Bacterial vaginosis who self-collected vaginal swabs daily over 60 days. We inferred Bacterial concentrations by taking the product of species relative abundance (assessed by 16S rRNA gene amplicon sequencing) and Bacterial Load (measured by broad-range 16S rRNA gene qPCR). Log10-converted inferred concentrations correlated with targeted qPCR (r = 0. 935, P 0.5-log10 errors occurred when the relative abundance was 10%, inferred concentrations are reliable proxies for targeted qPCR in the vaginal microbiome. However, targeted qPCR is required to capture bacteria at low relative abundance and is preferable for characterizing growth and decay kinetics of single species. IMPORTANCE Microbiome studies primarily use 16S rRNA gene amplicon sequencing to assess the relative abundance of Bacterial taxa in a community. However, these measurements do not accurately reflect absolute taxon concentrations. We sought to determine whether the product of species’ relative abundance and total Bacterial Load measured by broad-range qPCR is an accurate proxy for individual species’ concentrations, as measured by taxon-specific qPCR assays. Overall, the inferred Bacterial concentrations were a reasonable proxy of species-specific qPCR values, particularly when bacteria are present at a higher relative abundance. This approach offers an opportunity to assess the concentrations of Bacterial species and how they change in a community over time without developing individual qPCR assays for each taxon.

  • complementing 16s rrna gene amplicon sequencing with estimates of total Bacterial Load to infer absolute species concentrations in the vaginal microbiome
    bioRxiv, 2019
    Co-Authors: Florencia Tettamanti A Boshier, Sujatha Srinivasan, Anthony Lopez, Noah G Hoffman, Sean Proll, David N Fredricks, Joshua T Schiffer
    Abstract:

    Whereas 16S rRNA gene amplicon sequencing quantifies relative abundances of Bacterial taxa, variation in total Bacterial Load between samples restricts its ability to reflect absolute concentration of individual species. Quantitative PCR (qPCR) can quantify individual species, but it is not practical to develop a suite of qPCR assays for every bacterium present in a diverse sample. We analyzed 1320 samples from 20 women with a history of frequent Bacterial vaginosis, who self-collected vaginal swabs daily over 60 days. We inferred Bacterial concentrations by taking the product of species relative abundance (assessed by 16S rRNA gene amplicon sequencing) and total Bacterial Load (measured by broad-range 16S rRNA gene qPCR). Log10-converted inferred concentrations correlated with targeted qPCR (r = 0. 935, p 0.5 log10 occurred when relative abundance was 10%, inferred concentrations are reliable proxies for targeted qPCR. However, targeted qPCR is required to capture bacteria at low relative abundance, particularly with BV-associated bacteria during the early onset of Bacterial vaginosis.

Nguyen Thuy Thuong Thuong - One of the best experts on this subject based on the ideXlab platform.

  • comparison of the mycobacterium tuberculosis molecular Bacterial Load assay microscopy and genexpert versus liquid culture for viable Bacterial Load quantification before and after starting pulmonary tuberculosis treatment
    Tuberculosis, 2019
    Co-Authors: Hoang T Hai, Dao N Vinh, Do Dang Anh Thu, Nguyen T Hanh, Nguyen Hoan Phu, Vijay Srinivasan, Guy Thwaites, Nguyen Thuy Thuong Thuong
    Abstract:

    Abstract Molecular Bacterial Load assay (MBLA) rapidly quantifies viable Mycobacterium tuberculosis (Mtb) and may be useful for monitoring treatment response and treatment efficacy. We conducted a prospective study in 56 adults with pulmonary tuberculosis from whom 244 sputum samples were collected before and during the first month of treatment. We evaluated MBLA for early monitoring of Bacterial burden and investigated bactericidal activities of first-line therapy in patients infected with drug susceptible and resistant isolates. Mtb Loads measured by MBLA and culture were correlated after one-week (r = 0.56) and one-month (r = 0.73) of treatment. Correlations between culture and GeneXpert or microscopy were weaker during treatment. Mtb Load by MBLA declined more rapidly than GeneXpert after one-week (2.73 Ct, P  MBLA performed better than GeneXpert and microscopy in comparison to culture for quantifying viable Mtb during treatment. It can be used for monitoring Bacterial Load during TB treatment, facilitating early detection of treatment failure thus improving outcomes.

  • pretreatment cerebrospinal fluid Bacterial Load correlates with inflammatory response and predicts neurological events during tuberculous meningitis treatment
    The Journal of Infectious Diseases, 2019
    Co-Authors: Nguyen Thuy Thuong Thuong, Hoang T Hai, Dao N Vinh, Do Dang Anh Thu, Le Thanh Hoang Nhat, Dorothee Heemskerk, Nguyen Duc Bang, Maxine Caws, Nguyen Thi Hoang Mai
    Abstract:

    BACKGROUND The Mycobacterium tuberculosis Load in the brain of individuals with tuberculous meningitis (TBM) may reflect the host's ability to control the pathogen, determine disease severity, and determine treatment outcomes. METHODS We used the GeneXpert assay to measure the pretreatment M. tuberculosis Load in cerebrospinal fluid (CSF) specimens from 692 adults with TBM. We sought to understand the relationship between CSF Bacterial Load and inflammation, and their respective impact on disease severity and treatment outcomes. RESULTS A 10-fold higher M. tuberculosis Load was associated with increased disease severity (odds ratio, 1.59; P = .001 for the comparison between grade 1 and grade 3 severity), CSF neutrophil count (r = 0.364 and P < .0001), and cytokine concentrations (r = 0.438 and P < .0001). A high M. tuberculosis Load predicted new neurological events after starting treatment (P = .005, by multinomial logistic regression) but not death. Patients who died had an attenuated inflammatory response at the start of treatment, with reduced cytokine concentrations as compared to survivors. In contrast, patients with high pretreatment CSF Bacterial Loads, cytokine concentrations, and neutrophil counts were more likely to subsequently experience neurological events. CONCLUSIONS The pretreatment GeneXpert-determined M. tuberculosis Load may be a useful predictor of neurological complications occurring during TBM treatment. Given the evidence for the divergent pathogenesis of TBM-associated neurological complications and deaths, therapeutic strategies to reduce them may need reassessment.