Effect of Standard Tuberculosis Treatment on Plasma Cytokine Levels in Patients with Active Pulmonary Tuberculosis
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{"title"=>"Effect of standard tuberculosis treatment on plasma cytokine levels in patients with active pulmonary tuberculosis", "type"=>"journal", "authors"=>[{"first_name"=>"Catherine", "last_name"=>"Riou", "scopus_author_id"=>"14028976400"}, {"first_name"=>"Blas", "last_name"=>"Perez Peixoto", "scopus_author_id"=>"55216585100"}, {"first_name"=>"Lindi", "last_name"=>"Roberts", "scopus_author_id"=>"35389600600"}, {"first_name"=>"Katharina", "last_name"=>"Ronacher", "scopus_author_id"=>"24528688300"}, {"first_name"=>"Gerhard", "last_name"=>"Walzl", "scopus_author_id"=>"56050296500"}, {"first_name"=>"Claudia", "last_name"=>"Manca", "scopus_author_id"=>"7005502232"}, {"first_name"=>"Roxana", "last_name"=>"Rustomjee", "scopus_author_id"=>"18937137600"}, {"first_name"=>"Thuli", "last_name"=>"Mthiyane", "scopus_author_id"=>"6507884687"}, {"first_name"=>"Dorothy", "last_name"=>"Fallows", "scopus_author_id"=>"6507558810"}, {"first_name"=>"Clive M.", "last_name"=>"Gray", "scopus_author_id"=>"7402204152"}, {"first_name"=>"Gilla", "last_name"=>"Kaplan", "scopus_author_id"=>"7201362969"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"22606304", "doi"=>"10.1371/journal.pone.0036886", "sgr"=>"84861007077", "isbn"=>"10.1371/journal.pone.0036886", "scopus"=>"2-s2.0-84861007077", "issn"=>"19326203", "pui"=>"364803153"}, "id"=>"1a8ca82b-b360-3c47-b691-ff0b98801746", "abstract"=>"BACKGROUND: Sputum Mycobacterium tuberculosis (Mtb) culture is commonly used to assess response to antibiotic treatment in individuals with pulmonary tuberculosis (TB). Such techniques are constrained by the slow growth rate of Mtb, and more sensitive methods to monitor Mtb clearance are needed. The goal of this study was to evaluate changes in plasma cytokines in patients undergoing treatment for TB as a means of identifying candidate host markers associated with microbiologic response to therapy.\\n\\nMETHODS: Twenty-four plasma cytokines/chemokines were measured in 42 individuals diagnosed with active pulmonary TB, 52% were HIV co-infected. Individuals, undergoing a 26-week standard TB treatment, were followed longitudinally over 18 months and measurements were associated with HIV status and rates of sputum culture conversion.\\n\\nRESULTS: Plasma concentrations of interferon-inducible protein-10 (IP-10) and vascular endothelial growth factor (VEGF) were significantly reduced upon TB treatment, regardless of HIV status. By the end of treatment, IP-10 concentrations were significantly lower in HIV negative individuals when compared to HIV-positive individuals (p = 0.02). Moreover, in HIV negative patients, plasma VEGF concentrations, measured as early as 2-weeks post TB treatment initiation, positively correlated with the time of sputum conversion (p = 0.0017). No significant changes were observed in other studied immune mediators.\\n\\nCONCLUSIONS: These data suggest that VEGF plasma concentration, measured during early TB treatment, could represent a surrogate marker to monitor sputum culture conversion in HIV uninfected individuals.", "link"=>"http://www.mendeley.com/research/effect-standard-tuberculosis-treatment-plasma-cytokine-levels-patients-active-pulmonary-tuberculosis", "reader_count"=>50, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Student > Doctoral Student"=>7, "Researcher"=>13, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>5, "Student > Master"=>11, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Student > Doctoral Student"=>7, "Researcher"=>13, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>5, "Student > Master"=>11, "Lecturer > Senior Lecturer"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>21, "Medicine and Dentistry"=>21, "Computer Science"=>1, "Immunology and Microbiology"=>5}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>21}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>21}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Argentina"=>1, "Denmark"=>1, "United Kingdom"=>1, "South Africa"=>1, "France"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/639050"], "description"=>"<p>− <b>and TB+HIV+ individuals.</b> (<b>A</b>) Two-dimensional unsupervised hierarchical clustering of baseline cytokine profiles in TB+HIV− (n = 20) and TB+HIV+ (n = 22) subjects. The normalized values for each cytokine are depicted according to the color scale, where red and green represent expression above and below the median, respectively. (<b>B</b>) Three-dimensional representation of principal component analysis (PCA) of HIV− (red) and HIV+ (green) individuals. Each dot represents one subject based on values of all 23 cytokines studied. The percentage of variances is depicted on the 3 axes. The distance in space between each dot represents the relatedness between each individual.</p>", "links"=>[], "tags"=>["profiles", "baseline", "plasma", "cytokines"], "article_id"=>309531, "categories"=>["Cell Biology", "Infectious Diseases", "Immunology"], "users"=>["Catherine Riou", "Blas Perez Peixoto", "Lindi Roberts", "Katharina Ronacher", "Gerhard Walzl", "Claudia Manca", "Roxana Rustomjee", "Thuli Mthiyane", "Dorothy Fallows", "Clive M. Gray", "Gilla Kaplan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036886.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_profiles_of_baseline_plasma_cytokines_in_TB_HIV_/309531", "title"=>"Expression profiles of baseline plasma cytokines in TB+HIV", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-14 02:38:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/638847"], "description"=>"<p>− <b>and TB+HIV+ individuals.</b> (<b>A</b>) Mediators endowed with pro- and anti-inflammatory functions. (<b>B</b>) Mediators endowed with pleiotropic, chemoattractant and growth functions. Results are expressed as pg/ml of plasma. Open circles represent TB+HIV− subjects (n = 20) and black circles correspond to TB+HIV+ subjects (n = 22). Dotted lines represent the average limit of detection for all cytokines. Statistical comparisons have been performed using non-parametric Mann-Whitney U test and corrected for multiple comparisons using a false discovery rate (FDR) step down procedure.</p>", "links"=>[], "tags"=>["baseline", "levels", "soluble", "plasma", "mediators"], "article_id"=>309324, "categories"=>["Cell Biology", "Infectious Diseases", "Immunology"], "users"=>["Catherine Riou", "Blas Perez Peixoto", "Lindi Roberts", "Katharina Ronacher", "Gerhard Walzl", "Claudia Manca", "Roxana Rustomjee", "Thuli Mthiyane", "Dorothy Fallows", "Clive M. Gray", "Gilla Kaplan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036886.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_baseline_expression_levels_of_soluble_plasma_mediators_between_TB_HIV_/309324", "title"=>"Comparison of baseline expression levels of soluble plasma mediators between TB+HIV", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-14 02:35:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/329859", "https://ndownloader.figshare.com/files/329934"], "description"=>"<div><h3>Background</h3><p>Sputum <em>Mycobacterium tuberculosis</em> (Mtb) culture is commonly used to assess response to antibiotic treatment in individuals with pulmonary tuberculosis (TB). Such techniques are constrained by the slow growth rate of Mtb, and more sensitive methods to monitor Mtb clearance are needed. The goal of this study was to evaluate changes in plasma cytokines in patients undergoing treatment for TB as a means of identifying candidate host markers associated with microbiologic response to therapy.</p> <h3>Methods</h3><p>Twenty-four plasma cytokines/chemokines were measured in 42 individuals diagnosed with active pulmonary TB, 52% were HIV co-infected. Individuals, undergoing a 26-week standard TB treatment, were followed longitudinally over 18 months and measurements were associated with HIV status and rates of sputum culture conversion.</p> <h3>Results</h3><p>Plasma concentrations of interferon-inducible protein-10 (IP-10) and vascular endothelial growth factor (VEGF) were significantly reduced upon TB treatment, regardless of HIV status. By the end of treatment, IP-10 concentrations were significantly lower in HIV negative individuals when compared to HIV-positive individuals (p = 0.02). Moreover, in HIV negative patients, plasma VEGF concentrations, measured as early as 2-weeks post TB treatment initiation, positively correlated with the time of sputum conversion (p = 0.0017). No significant changes were observed in other studied immune mediators.</p> <h3>Conclusions</h3><p>These data suggest that VEGF plasma concentration, measured during early TB treatment, could represent a surrogate marker to monitor sputum culture conversion in HIV uninfected individuals.</p> </div>", "links"=>[], "tags"=>["tuberculosis", "plasma", "cytokine", "levels", "patients", "pulmonary"], "article_id"=>125128, "categories"=>["Cancer", "Cell Biology", "Immunology"], "users"=>["Catherine Riou", "Blas Perez Peixoto", "Lindi Roberts", "Katharina Ronacher", "Gerhard Walzl", "Claudia Manca", "Roxana Rustomjee", "Thuli Mthiyane", "Dorothy Fallows", "Clive M. Gray", "Gilla Kaplan"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0036886.s001", "https://dx.doi.org/10.1371/journal.pone.0036886.s002"], "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Effect_of_Standard_Tuberculosis_Treatment_on_Plasma_Cytokine_Levels_in_Patients_with_Active_Pulmonary_Tuberculosis/125128", "title"=>"Effect of Standard Tuberculosis Treatment on Plasma Cytokine Levels in Patients with Active Pulmonary Tuberculosis", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-05-14 01:25:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/639660"], "description"=>"<p>M: Male, F: Female.</p>a<p>: 1: No cavities; 2: cavities <4 cm; 3: cavities ≥4 cm.</p><p>BMI: Body mass index.</p><p>nd: not determined.</p>b<p>: The time of conversion is defined as the first analyzed time point where culture was negative and remained negative at all following time points. Studied individuals were divided into 3 groups according to the time of sputum culture conversion: ≤ 8 weeks, between 12 and 26 weeks and > 26 weeks after the initiation of TB therapy.</p>", "links"=>[], "tags"=>["characteristics", "individuals"], "article_id"=>310146, "categories"=>["Cell Biology", "Infectious Diseases", "Immunology"], "users"=>["Catherine Riou", "Blas Perez Peixoto", "Lindi Roberts", "Katharina Ronacher", "Gerhard Walzl", "Claudia Manca", "Roxana Rustomjee", "Thuli Mthiyane", "Dorothy Fallows", "Clive M. Gray", "Gilla Kaplan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036886.t002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_characteristics_of_HIV_TB_individuals_n_8202_8202_22_/310146", "title"=>"Clinical characteristics of HIV+TB+ individuals (n = 22).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-05-14 00:02:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/639520"], "description"=>"<p>(<b>A</b>) TB+HIV− individuals; (<b>B</b>) TB+HIV+ individuals. VEGF concentration values were log-transformed. Statistical associations were performed by a two-tailed non-parametric Spearman rank correlation.</p>", "links"=>[], "tags"=>["plasma", "vegf", "concentrations", "weeks", "tb", "initiation", "sputum"], "article_id"=>309999, "categories"=>["Cell Biology", "Infectious Diseases", "Immunology"], "users"=>["Catherine Riou", "Blas Perez Peixoto", "Lindi Roberts", "Katharina Ronacher", "Gerhard Walzl", "Claudia Manca", "Roxana Rustomjee", "Thuli Mthiyane", "Dorothy Fallows", "Clive M. Gray", "Gilla Kaplan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036886.g005", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Correlation_between_plasma_VEGF_concentrations_at_2_weeks_post_TB_therapy_initiation_and_time_to_sputum_culture_conversion_/309999", "title"=>"Correlation between plasma VEGF concentrations at 2 weeks post TB therapy initiation and time to sputum culture conversion.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-14 02:46:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/639623"], "description"=>"<p>M: Male, F: Female.</p>a<p>: 1: No cavities ; 2: cavities <4 cm ; 3: cavities ≥4 cm.</p><p>BMI: Body mass index.</p><p>nd: not determined.</p>b<p>: The time of conversion is defined as the first analyzed time point where culture was negative and remained negative at all following time points. Studied individuals were divided into 3 groups according to the time of sputum culture conversion: ≤ 8 weeks, between 12 and 26 weeks and > 26 weeks after the initiation of TB therapy.</p>", "links"=>[], "tags"=>["characteristics", "individuals"], "article_id"=>310107, "categories"=>["Cell Biology", "Infectious Diseases", "Immunology"], "users"=>["Catherine Riou", "Blas Perez Peixoto", "Lindi Roberts", "Katharina Ronacher", "Gerhard Walzl", "Claudia Manca", "Roxana Rustomjee", "Thuli Mthiyane", "Dorothy Fallows", "Clive M. Gray", "Gilla Kaplan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036886.t001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_characteristics_of_HIV_8722_TB_individuals_n_8202_8202_20_/310107", "title"=>"Clinical characteristics of HIV−TB+ individuals (n = 20).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-05-14 00:01:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/639398"], "description"=>"<p>− <b>and TB+HIV+ individuals upon TB therapy.</b> (<b>A</b>) Longitudinal plasma IP-10 and VEGF concentrations before, during and after TB therapy in TB+HIV− (Red) and TB+HIV+ (Black) individuals. Values were log-transformed. Median values with 95% CI for TB+HIV− (n = 20) and TB+ HIV+ (n = 22) individuals are depicted in red and black, respectively. A shaded grey box represents the duration of TB therapy. Statistical analyses were performed using random-effects linear regression. (<b>B</b>) Comparison of fold-changes in plasma IP-10 and VEGF concentrations between baseline and 26-week measurements (end of TB therapy) in TB+HIV− and TB+HIV+ subjects. Each dot represents one individual. Open circles correspond to individuals who presented with sputum conversion at ≤8 weeks, closed circles correspond to individuals who presented with sputum culture conversion between 12 and 26 weeks after TB therapy initiation and crosses identify individuals where sputum culture conversion occurred after 26 weeks post treatment. Doted lines depict 50% and 80% reduction of cytokine expression levels. Statistical analyses were performed using non-parametric Mann-Whitney U test.</p>", "links"=>[], "tags"=>["ip-10", "vegf"], "article_id"=>309881, "categories"=>["Cell Biology", "Infectious Diseases", "Immunology"], "users"=>["Catherine Riou", "Blas Perez Peixoto", "Lindi Roberts", "Katharina Ronacher", "Gerhard Walzl", "Claudia Manca", "Roxana Rustomjee", "Thuli Mthiyane", "Dorothy Fallows", "Clive M. Gray", "Gilla Kaplan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036886.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_the_decrease_rate_of_IP_10_and_VEGF_in_TB_HIV_/309881", "title"=>"Comparison of the decrease rate of IP-10 and VEGF in TB+HIV", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-14 02:44:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/639211"], "description"=>"<p>− <b>individuals.</b> The concentration of each cytokine has been measured at baseline, 2, 4, 8, 12, 26, 52, 78 weeks after the initiation of a 26- week treatment period. Individuals who presented with sputum conversion at ≤8 weeks are depicted in red, individual who presented with sputum culture conversion between 12 and 26 weeks are depicted in blue and individuals where sputum culture conversion occurred after 26 weeks of TB therapy are shown in green. (<b>A</b>) Plasma cytokine levels (IL-2, IL-5, IL-13, G-CSF, IL-12, PDGF-BB, IL-7, IL-9, IFN-γ, MIP-1β, IL-4 and IL-10) showing no significant change overtime. (<b>B</b>) Plasma cytokine levels (IL-1RA, IL-6, Eotaxin, FGF-basic, IL-17, TNF-α, GM-CSF, MCP-1, IL-1β and IL-15) fluctuating overtime. (<b>C</b>) Plasma cytokines (IP-10 and VEGF) presenting significant changes over time. Each dot represents one individual (n = 20). Results are expressed as pg/ml of plasma. Dotted lines represent the limit of detection for each cytokine. Gray shaded box (on the first graph) represents the duration of TB therapy; dark gray box depicts the intensive phase of treatment, including rifampicin, isoniazid, pyrazinamide and ethambutol, while light gray box corresponds to the second phase of treatment with rifampicin and isoniazid. Statistical analyses were performed using non-parametric one-way ANOVA Kruskal-Wallis Tests (*: p<0.05, **: p<0.01, ***: P<0.001). Numerical p-values, reflecting the overall changes in IP-10 and VEGF expression levels, have been determined using random-effects linear regression. The <i>x</i>-axis (time after the initiation of treatment in weeks) has been logged to allow better visualization of cytokine expression levels at early time points.</p>", "links"=>[], "tags"=>["plasma", "cytokine", "levels", "tb"], "article_id"=>309695, "categories"=>["Cell Biology", "Infectious Diseases", "Immunology"], "users"=>["Catherine Riou", "Blas Perez Peixoto", "Lindi Roberts", "Katharina Ronacher", "Gerhard Walzl", "Claudia Manca", "Roxana Rustomjee", "Thuli Mthiyane", "Dorothy Fallows", "Clive M. Gray", "Gilla Kaplan"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036886.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Longitudinal_assessment_of_plasma_cytokine_expression_levels_before_during_and_after_TB_therapy_in_TB_HIV_/309695", "title"=>"Longitudinal assessment of plasma cytokine expression levels before, during and after TB therapy in TB+HIV", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-05-14 02:41:35"}

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Relative Metric

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