Clinical Diagnostic Utility of IP-10 and LAM Antigen Levels for the Diagnosis of Tuberculous Pleural Effusions in a High Burden Setting
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{"title"=>"Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting", "type"=>"journal", "authors"=>[{"first_name"=>"Keertan", "last_name"=>"Dheda", "scopus_author_id"=>"6701576021"}, {"first_name"=>"Richard N.", "last_name"=>"Van-Zyl Smit", "scopus_author_id"=>"6603972670"}, {"first_name"=>"Leonardo A.", "last_name"=>"Sechi", "scopus_author_id"=>"35480017300"}, {"first_name"=>"Motasim", "last_name"=>"Badri", "scopus_author_id"=>"7005213070"}, {"first_name"=>"Richard", "last_name"=>"Meldau", "scopus_author_id"=>"26421747300"}, {"first_name"=>"Gregory", "last_name"=>"Symons", "scopus_author_id"=>"26421870300"}, {"first_name"=>"Hoosein", "last_name"=>"Khalfey", "scopus_author_id"=>"55538849100"}, {"first_name"=>"Igshaan", "last_name"=>"Carr", "scopus_author_id"=>"26421624900"}, {"first_name"=>"Alice", "last_name"=>"Maredza", "scopus_author_id"=>"8751983600"}, {"first_name"=>"Rodney", "last_name"=>"Dawson", "scopus_author_id"=>"24471532800"}, {"first_name"=>"Helen", "last_name"=>"Wainright", "scopus_author_id"=>"26421855100"}, {"first_name"=>"Andrew", "last_name"=>"Whitelaw", "scopus_author_id"=>"35235416900"}, {"first_name"=>"Eric D.", "last_name"=>"Bateman", "scopus_author_id"=>"7005609363"}, {"first_name"=>"Alimuddin", "last_name"=>"Zumla", "scopus_author_id"=>"7006170723"}], "year"=>2009, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"62849089035", "doi"=>"10.1371/journal.pone.0004689", "pui"=>"354352423", "pmid"=>"19277111", "scopus"=>"2-s2.0-62849089035", "issn"=>"19326203", "isbn"=>"1932-6203"}, "id"=>"dff704c6-4ee4-31be-8bd7-2b00ee8f3f13", "abstract"=>"BACKGROUND: Current tools for the diagnosis of tuberculosis pleural effusions are sub-optimal. Data about the value of new diagnostic technologies are limited, particularly, in high burden settings. Preliminary case control studies have identified IFN-gamma-inducible-10 kDa protein (IP-10) as a promising diagnostic marker; however, its diagnostic utility in a day-to-day clinical setting is unclear. Detection of LAM antigen has not previously been evaluated in pleural fluid.\\n\\nMETHODS: We investigated the comparative diagnostic utility of established (adenosine deaminase [ADA]), more recent (standardized nucleic-acid-amplification-test [NAAT]) and newer technologies (a standardized LAM mycobacterial antigen-detection assay and IP-10 levels) for the evaluation of pleural effusions in 78 consecutively recruited South African tuberculosis suspects. All consenting participants underwent pleural biopsy unless contra-indicated or refused. The reference standard comprised culture positivity for M. tuberculosis or histology suggestive of tuberculosis.\\n\\nPRINCIPAL FINDINGS: Of 74 evaluable subjects 48, 7 and 19 had definite, probable and non-TB, respectively. IP-10 levels were significantly higher in TB vs non-TB participants (p<0.0001). The respective outcomes [sensitivity, specificity, PPV, NPV %] for the different diagnostic modalities were: ADA at the 30 IU/L cut-point [96; 69; 90; 85], NAAT [6; 93; 67; 28], IP-10 at the 28,170 pg/ml ROC-derived cut-point [80; 82; 91; 64], and IP-10 at the 4035 pg/ml cut-point [100; 53; 83; 100]. Thus IP-10, using the ROC-derived cut-point, missed approximately 20% of TB cases and mis-diagnosed approximately 20% of non-TB cases. By contrast, when a lower cut-point was used a negative test excluded TB. The NAAT had a poor sensitivity but high specificity. LAM antigen-detection was not diagnostically useful.\\n\\nCONCLUSION: Although IP-10, like ADA, has sub-optimal specificity, it may be a clinically useful rule-out test for tuberculous pleural effusions. Larger multi-centric studies are now required to confirm our findings.", "link"=>"http://www.mendeley.com/research/clinical-diagnostic-utility-ip10-lam-antigen-levels-diagnosis-tuberculous-pleural-effusions-high-bur-5", "reader_count"=>40, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Researcher"=>9, "Student > Doctoral Student"=>6, "Student > Ph. D. Student"=>8, "Other"=>2, "Student > Master"=>2, "Student > Bachelor"=>5, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Researcher"=>9, "Student > Doctoral Student"=>6, "Student > Ph. D. Student"=>8, "Other"=>2, "Student > Master"=>2, "Student > Bachelor"=>5, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>19, "Agricultural and Biological Sciences"=>16, "Chemistry"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>19}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Egypt"=>1, "Brazil"=>1, "Switzerland"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/905256"], "description"=>"<p>Summary and flow chart of the established and newer technologies evaluated.</p>", "links"=>[], "tags"=>["established", "newer", "technologies"], "article_id"=>575693, "categories"=>["Medicine", "Infectious Diseases"], "users"=>["Keertan Dheda", "Richard N. Van-Zyl Smit", "Leonardo A. Sechi", "Motasim Badri", "Richard Meldau", "Gregory Symons", "Hoosein Khalfey", "Igshaan Carr", "Alice Maredza", "Rodney Dawson", "Helen Wainright", "Andrew Whitelaw", "Eric D. Bateman", "Alimuddin Zumla"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004689.g001", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_and_flow_chart_of_the_established_and_newer_technologies_evaluated_/575693", "title"=>"Summary and flow chart of the established and newer technologies evaluated.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 06:35:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/905380"], "description"=>"<p>Area under the ROC values are shown in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004689#pone-0004689-t001\" target=\"_blank\">table 1</a>. Positive (culture and amplification) and negative controls (culture and amplification) from 6 independent runs are shown.</p>", "links"=>[], "tags"=>["roc", "standardized", "nucleic-acid", "amplification", "pleural", "patients", "tuberculous", "non-tuberculous"], "article_id"=>575812, "categories"=>["Medicine", "Infectious Diseases"], "users"=>["Keertan Dheda", "Richard N. Van-Zyl Smit", "Leonardo A. Sechi", "Motasim Badri", "Richard Meldau", "Gregory Symons", "Hoosein Khalfey", "Igshaan Carr", "Alice Maredza", "Rodney Dawson", "Helen Wainright", "Andrew Whitelaw", "Eric D. Bateman", "Alimuddin Zumla"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004689.g002", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Scatter_plots_left_panel_and_area_under_the_ROC_right_panel_of_a_standardized_nucleic_acid_amplification_test_using_pleural_fluid_from_patients_with_tuberculous_TB_and_non_tuberculous_non_TB_effusions_/575812", "title"=>"Scatter-plots (left panel) and area under the ROC (right panel) of a standardized nucleic-acid amplification test using pleural fluid from patients with tuberculous (TB) and non-tuberculous (non-TB) effusions.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 06:35:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/905581"], "description"=>"<p>( ; ) = 95% CI.</p>**<p>Cut-point used in day-to-day clinical practice in Cape Town, South Africa, where the test guides the institution of anti-TB treatment.</p><p>AUC = area under the ROC curve.</p>***<p>AUC-derived cut-point.</p>#<p>cut-point with a high NPV.</p><p>RLU = relative light units detectable using a luminometer.</p>", "links"=>[], "tags"=>["outcomes", "microbiological", "nucleic-acid-amplification-test", "unstimulated", "levels", "tb", "pleural", "effusion", "74", "suspects"], "article_id"=>576014, "categories"=>["Medicine", "Infectious Diseases"], "users"=>["Keertan Dheda", "Richard N. Van-Zyl Smit", "Leonardo A. Sechi", "Motasim Badri", "Richard Meldau", "Gregory Symons", "Hoosein Khalfey", "Igshaan Carr", "Alice Maredza", "Rodney Dawson", "Helen Wainright", "Andrew Whitelaw", "Eric D. Bateman", "Alimuddin Zumla"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004689.t001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Performance_outcomes_of_ADA_microbiological_investigations_a_nucleic_acid_amplification_test_NAAT_and_unstimulated_IFN_levels_for_the_diagnosis_of_TB_pleural_effusion_in_74_TB_suspects_using_the_definite_and_non_TB_groups_/576014", "title"=>"Performance outcomes of ADA, microbiological investigations, a nucleic-acid-amplification-test [NAAT] and unstimulated IFN-γ levels for the diagnosis of TB pleural effusion in 74 TB suspects using the <i>definite and non-TB</i> groups.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 06:36:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/905630"], "description"=>"*<p> = 47 iu/l cut-point and non-asterisked values refer to the 30 iu/l cut-point.</p>$<p> = maximal clinical score. Unless, otherwise stated all IP-10 outcomes refer to the 28170 pg/ml cut-point.</p>", "links"=>[], "tags"=>["incremental"], "article_id"=>576075, "categories"=>["Medicine", "Infectious Diseases"], "users"=>["Keertan Dheda", "Richard N. Van-Zyl Smit", "Leonardo A. Sechi", "Motasim Badri", "Richard Meldau", "Gregory Symons", "Hoosein Khalfey", "Igshaan Carr", "Alice Maredza", "Rodney Dawson", "Helen Wainright", "Andrew Whitelaw", "Eric D. Bateman", "Alimuddin Zumla"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004689.t003", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Individual_and_incremental_value_of_different_test_combinations_/576075", "title"=>"Individual and incremental value of different test combinations.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 06:37:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/905689"], "description"=>"<p>( ; ) = 95% CI.</p>**<p>Cut-point used in day-to-day clinical practice in Cape Town, South Africa, where the test guides the institution of anti-TB treatment.</p><p>AUC = area under the ROC curve.</p>***<p>AUC-derived cut-point.</p>#<p>cut-point with a high NPV.</p><p>RLU = relative light units detectable using a luminometer.</p>", "links"=>[], "tags"=>["outcomes", "microbiological", "nucleic-acid-amplification-test", "unstimulated", "levels", "tb", "pleural", "effusion", "74", "suspects", "probable", "groups"], "article_id"=>576121, "categories"=>["Medicine", "Infectious Diseases"], "users"=>["Keertan Dheda", "Richard N. Van-Zyl Smit", "Leonardo A. Sechi", "Motasim Badri", "Richard Meldau", "Gregory Symons", "Hoosein Khalfey", "Igshaan Carr", "Alice Maredza", "Rodney Dawson", "Helen Wainright", "Andrew Whitelaw", "Eric D. Bateman", "Alimuddin Zumla"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004689.t002", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Performance_outcomes_of_ADA_microbiological_investigations_a_nucleic_acid_amplification_test_NAAT_and_unstimulated_IFN_levels_for_the_diagnosis_of_TB_pleural_effusion_in_74_TB_suspects_when_the_definite_and_probable_TB_groups_are_combined_/576121", "title"=>"Performance outcomes of ADA, microbiological investigations, a nucleic-acid-amplification-test [NAAT] and unstimulated IFN-γ levels for the diagnosis of TB pleural effusion in 74 TB suspects when the <i>definite and probable TB groups are combined</i>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 06:37:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/905467"], "description"=>"<p>The area under the ROC curve was 0.82.</p>", "links"=>[], "tags"=>["ip-10", "levels", "patients", "pleural", "tuberculosis", "non-tuberculosis"], "article_id"=>575908, "categories"=>["Medicine", "Infectious Diseases"], "users"=>["Keertan Dheda", "Richard N. Van-Zyl Smit", "Leonardo A. Sechi", "Motasim Badri", "Richard Meldau", "Gregory Symons", "Hoosein Khalfey", "Igshaan Carr", "Alice Maredza", "Rodney Dawson", "Helen Wainright", "Andrew Whitelaw", "Eric D. Bateman", "Alimuddin Zumla"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0004689.g003", "stats"=>{"downloads"=>1, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Scatter_plot_left_panel_showing_IP_10_levels_in_patients_with_pleural_tuberculosis_versus_non_tuberculosis_controls_/575908", "title"=>"Scatter-plot (left panel) showing IP-10 levels in patients with pleural tuberculosis versus non-tuberculosis controls.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 06:36:21"}

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  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
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  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
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  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
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  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"15", "full-text"=>"16", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"2", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"5", "full-text"=>"7", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
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Relative Metric

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