@article{Macpherson2024,
abstract = {Background WHO Tuberculosis (TB) screening guidelines recommend computer-aided detection (CAD) software for chest radiograph (CXR) interpretation. However, studies evaluating their diagnostic and prognostic accuracy are limited. Methods We conducted a prospective cohort study of household TB contacts in South Africa. Participants all underwent baseline CXR and sputum investigation (routine [single spontaneous] and enhanced [additionally 2-3 induced] sputum investigation and passive and active follow-up for incident TB. CXR were processed comparing 3 CAD softwares (CAD4TBv7.0, qXRv3.0.0, and Lunit INSIGHT CXR 3.1.4.111). We evaluated their performance to detect routine and enhanced prevalent, and incident TB, comparing the performance to blood-based biomarkers (Xpert MTB host-response, Erythrocyte Sedimentation Rate, C-Reactive Protein, QuantiFERON) in a subgroup. Findings 483 participants were followed-up for 4.6 years (median). There were 23 prevalent (7 routinely diagnosed) and 38 incident TB cases. The AUC ROC to identify prevalent TB for CAD4TB, qXR and Lunit INSIGHT CXR were 0.87 (95{\%} CI 0.77-0.96), 0.88 (95{\%} CI 0.79-0.97) and 0.91 (95{\%} CI 0.83-0.99) respectively. {\textgreater}30{\%} with scores above recommended CAD thresholds who were bacteriologically negative on routine baseline sputum were subsequently diagnosed by enhanced baseline sputum investigation or during follow-up. The AUC performance of baseline CAD to identify incident cases ranged between 0.60-0.65. The diagnostic performance of CAD for prevalent TB was superior to blood-based biomarkers. Interpretation Our findings suggest that the potential of CAD-CXR screening for TB is not maximised as a high proportion of those above current thresholds but with a negative routine confirmatory sputum have true TB disease that may benefit intervention. Funding UKRI-MRC Summary We found that the diagnostic accuracy of CAD-CXR to identify prevalent TB cases in household TB contacts was high but {\textgreater}30{\%} with scores above recommended CAD thresholds who were bacteriologically negative on routine testing baseline were subsequently diagnosed suggest that the potential of CAD-CXR screening is not maximised. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement This study was supported by an MRC award (Grant Ref: MR/V00476X/1) to HE. HE is partially supported by and MRC unit grant (MC UU 00004/04). AKC is partially supported by the NHMRC (GNT2020750) and WEHI. RJW is supported by the Francis Crick Institute which receives funding from Cancer Research Uk (FC2112), UK Research and Innovation-MRC (CC2112) and Wellcome (CC2112). He also receives funding from Wellcome (203135), South African MRC via its Strategic health Partnerships and the Bill and Melinda Gates Foundation. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committees of University of Cape Town (449/2014), Boston University (H-35831), Rutgers University (Pro2018001966), NIH (DMID 16-0112) and University College London (19219/001) gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors},
author = {Macpherson, Liana and Kik, Sandra V and Quartagno, Matteo and Lakay, Francisco and Jaftha, Marche and Yende, Nombuso and Galant, Shireen and Aziz, Saalikha and Daroowala, Remy and Court, Richard and Taliep, Arshad and Serole, Keboile and Goliath, Rene T and Davies, Nashreen Omar and Jackson, Amanda and Douglass, Emily and Sossen, Bianca and Mukasa, Sandra and Thienemann, Friedrich and Song, Taeksun and Ruhwald, Morten and Wilkinson, Robert J and Coussens, Anna K and Esmail, Hanif},
doi = {10.1101/2024.06.30.24309731},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Macpherson et al. - 2024 - Diagnostic accuracy of Chest X-Ray Computer Aided Detection software and blood biomarkers for detection of pr.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {jul},
pages = {2024.06.30.24309731},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Diagnostic accuracy of chest X-Ray Computer Aided Detection software and blood biomarkers for detection of prevalent and incident tuberculosis in household contacts followed up for 5 years}},
url = {https://www.medrxiv.org/content/10.1101/2024.06.30.24309731v1 https://www.medrxiv.org/content/10.1101/2024.06.30.24309731v1.abstract},
year = {2024}
}

{"_id":"LWoAHQa3MobFCZPxW","bibbaseid":"macpherson-kik-quartagno-lakay-jaftha-yende-galant-aziz-etal-diagnosticaccuracyofchestxraycomputeraideddetectionsoftwareandbloodbiomarkersfordetectionofprevalentandincidenttuberculosisinhouseholdcontactsfollowedupfor5years-2024","author_short":["Macpherson, L.","Kik, S. V","Quartagno, M.","Lakay, F.","Jaftha, M.","Yende, N.","Galant, S.","Aziz, S.","Daroowala, R.","Court, R.","Taliep, A.","Serole, K.","Goliath, R. T","Davies, N. O.","Jackson, A.","Douglass, E.","Sossen, B.","Mukasa, S.","Thienemann, F.","Song, T.","Ruhwald, M.","Wilkinson, R. J","Coussens, A. K","Esmail, H."],"bibdata":{"bibtype":"article","type":"article","abstract":"Background WHO Tuberculosis (TB) screening guidelines recommend computer-aided detection (CAD) software for chest radiograph (CXR) interpretation. However, studies evaluating their diagnostic and prognostic accuracy are limited. Methods We conducted a prospective cohort study of household TB contacts in South Africa. Participants all underwent baseline CXR and sputum investigation (routine [single spontaneous] and enhanced [additionally 2-3 induced] sputum investigation and passive and active follow-up for incident TB. CXR were processed comparing 3 CAD softwares (CAD4TBv7.0, qXRv3.0.0, and Lunit INSIGHT CXR 3.1.4.111). We evaluated their performance to detect routine and enhanced prevalent, and incident TB, comparing the performance to blood-based biomarkers (Xpert MTB host-response, Erythrocyte Sedimentation Rate, C-Reactive Protein, QuantiFERON) in a subgroup. Findings 483 participants were followed-up for 4.6 years (median). There were 23 prevalent (7 routinely diagnosed) and 38 incident TB cases. The AUC ROC to identify prevalent TB for CAD4TB, qXR and Lunit INSIGHT CXR were 0.87 (95% CI 0.77-0.96), 0.88 (95% CI 0.79-0.97) and 0.91 (95% CI 0.83-0.99) respectively. \\textgreater30% with scores above recommended CAD thresholds who were bacteriologically negative on routine baseline sputum were subsequently diagnosed by enhanced baseline sputum investigation or during follow-up. The AUC performance of baseline CAD to identify incident cases ranged between 0.60-0.65. The diagnostic performance of CAD for prevalent TB was superior to blood-based biomarkers. Interpretation Our findings suggest that the potential of CAD-CXR screening for TB is not maximised as a high proportion of those above current thresholds but with a negative routine confirmatory sputum have true TB disease that may benefit intervention. Funding UKRI-MRC Summary We found that the diagnostic accuracy of CAD-CXR to identify prevalent TB cases in household TB contacts was high but \\textgreater30% with scores above recommended CAD thresholds who were bacteriologically negative on routine testing baseline were subsequently diagnosed suggest that the potential of CAD-CXR screening is not maximised. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by an MRC award (Grant Ref: MR/V00476X/1) to HE. HE is partially supported by and MRC unit grant (MC UU 00004/04). AKC is partially supported by the NHMRC (GNT2020750) and WEHI. RJW is supported by the Francis Crick Institute which receives funding from Cancer Research Uk (FC2112), UK Research and Innovation-MRC (CC2112) and Wellcome (CC2112). He also receives funding from Wellcome (203135), South African MRC via its Strategic health Partnerships and the Bill and Melinda Gates Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committees of University of Cape Town (449/2014), Boston University (H-35831), Rutgers University (Pro2018001966), NIH (DMID 16-0112) and University College London (19219/001) gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors","author":[{"propositions":[],"lastnames":["Macpherson"],"firstnames":["Liana"],"suffixes":[]},{"propositions":[],"lastnames":["Kik"],"firstnames":["Sandra","V"],"suffixes":[]},{"propositions":[],"lastnames":["Quartagno"],"firstnames":["Matteo"],"suffixes":[]},{"propositions":[],"lastnames":["Lakay"],"firstnames":["Francisco"],"suffixes":[]},{"propositions":[],"lastnames":["Jaftha"],"firstnames":["Marche"],"suffixes":[]},{"propositions":[],"lastnames":["Yende"],"firstnames":["Nombuso"],"suffixes":[]},{"propositions":[],"lastnames":["Galant"],"firstnames":["Shireen"],"suffixes":[]},{"propositions":[],"lastnames":["Aziz"],"firstnames":["Saalikha"],"suffixes":[]},{"propositions":[],"lastnames":["Daroowala"],"firstnames":["Remy"],"suffixes":[]},{"propositions":[],"lastnames":["Court"],"firstnames":["Richard"],"suffixes":[]},{"propositions":[],"lastnames":["Taliep"],"firstnames":["Arshad"],"suffixes":[]},{"propositions":[],"lastnames":["Serole"],"firstnames":["Keboile"],"suffixes":[]},{"propositions":[],"lastnames":["Goliath"],"firstnames":["Rene","T"],"suffixes":[]},{"propositions":[],"lastnames":["Davies"],"firstnames":["Nashreen","Omar"],"suffixes":[]},{"propositions":[],"lastnames":["Jackson"],"firstnames":["Amanda"],"suffixes":[]},{"propositions":[],"lastnames":["Douglass"],"firstnames":["Emily"],"suffixes":[]},{"propositions":[],"lastnames":["Sossen"],"firstnames":["Bianca"],"suffixes":[]},{"propositions":[],"lastnames":["Mukasa"],"firstnames":["Sandra"],"suffixes":[]},{"propositions":[],"lastnames":["Thienemann"],"firstnames":["Friedrich"],"suffixes":[]},{"propositions":[],"lastnames":["Song"],"firstnames":["Taeksun"],"suffixes":[]},{"propositions":[],"lastnames":["Ruhwald"],"firstnames":["Morten"],"suffixes":[]},{"propositions":[],"lastnames":["Wilkinson"],"firstnames":["Robert","J"],"suffixes":[]},{"propositions":[],"lastnames":["Coussens"],"firstnames":["Anna","K"],"suffixes":[]},{"propositions":[],"lastnames":["Esmail"],"firstnames":["Hanif"],"suffixes":[]}],"doi":"10.1101/2024.06.30.24309731","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Macpherson et al. - 2024 - Diagnostic accuracy of Chest X-Ray Computer Aided Detection software and blood biomarkers for detection of pr.pdf:pdf","journal":"medRxiv","keywords":"OA,fund_ack,original","mendeley-tags":"OA,fund_ack,original","month":"jul","pages":"2024.06.30.24309731","publisher":"Cold Spring Harbor Laboratory Press","title":"Diagnostic accuracy of chest X-Ray Computer Aided Detection software and blood biomarkers for detection of prevalent and incident tuberculosis in household contacts followed up for 5 years","url":"https://www.medrxiv.org/content/10.1101/2024.06.30.24309731v1 https://www.medrxiv.org/content/10.1101/2024.06.30.24309731v1.abstract","year":"2024","bibtex":"@article{Macpherson2024,\r\nabstract = {Background WHO Tuberculosis (TB) screening guidelines recommend computer-aided detection (CAD) software for chest radiograph (CXR) interpretation. However, studies evaluating their diagnostic and prognostic accuracy are limited. Methods We conducted a prospective cohort study of household TB contacts in South Africa. Participants all underwent baseline CXR and sputum investigation (routine [single spontaneous] and enhanced [additionally 2-3 induced] sputum investigation and passive and active follow-up for incident TB. CXR were processed comparing 3 CAD softwares (CAD4TBv7.0, qXRv3.0.0, and Lunit INSIGHT CXR 3.1.4.111). We evaluated their performance to detect routine and enhanced prevalent, and incident TB, comparing the performance to blood-based biomarkers (Xpert MTB host-response, Erythrocyte Sedimentation Rate, C-Reactive Protein, QuantiFERON) in a subgroup. Findings 483 participants were followed-up for 4.6 years (median). There were 23 prevalent (7 routinely diagnosed) and 38 incident TB cases. The AUC ROC to identify prevalent TB for CAD4TB, qXR and Lunit INSIGHT CXR were 0.87 (95{\\%} CI 0.77-0.96), 0.88 (95{\\%} CI 0.79-0.97) and 0.91 (95{\\%} CI 0.83-0.99) respectively. {\\textgreater}30{\\%} with scores above recommended CAD thresholds who were bacteriologically negative on routine baseline sputum were subsequently diagnosed by enhanced baseline sputum investigation or during follow-up. The AUC performance of baseline CAD to identify incident cases ranged between 0.60-0.65. The diagnostic performance of CAD for prevalent TB was superior to blood-based biomarkers. Interpretation Our findings suggest that the potential of CAD-CXR screening for TB is not maximised as a high proportion of those above current thresholds but with a negative routine confirmatory sputum have true TB disease that may benefit intervention. Funding UKRI-MRC Summary We found that the diagnostic accuracy of CAD-CXR to identify prevalent TB cases in household TB contacts was high but {\\textgreater}30{\\%} with scores above recommended CAD thresholds who were bacteriologically negative on routine testing baseline were subsequently diagnosed suggest that the potential of CAD-CXR screening is not maximised. {\\#}{\\#}{\\#} Competing Interest Statement The authors have declared no competing interest. {\\#}{\\#}{\\#} Funding Statement This study was supported by an MRC award (Grant Ref: MR/V00476X/1) to HE. HE is partially supported by and MRC unit grant (MC UU 00004/04). AKC is partially supported by the NHMRC (GNT2020750) and WEHI. RJW is supported by the Francis Crick Institute which receives funding from Cancer Research Uk (FC2112), UK Research and Innovation-MRC (CC2112) and Wellcome (CC2112). He also receives funding from Wellcome (203135), South African MRC via its Strategic health Partnerships and the Bill and Melinda Gates Foundation. {\\#}{\\#}{\\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committees of University of Cape Town (449/2014), Boston University (H-35831), Rutgers University (Pro2018001966), NIH (DMID 16-0112) and University College London (19219/001) gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors},\r\nauthor = {Macpherson, Liana and Kik, Sandra V and Quartagno, Matteo and Lakay, Francisco and Jaftha, Marche and Yende, Nombuso and Galant, Shireen and Aziz, Saalikha and Daroowala, Remy and Court, Richard and Taliep, Arshad and Serole, Keboile and Goliath, Rene T and Davies, Nashreen Omar and Jackson, Amanda and Douglass, Emily and Sossen, Bianca and Mukasa, Sandra and Thienemann, Friedrich and Song, Taeksun and Ruhwald, Morten and Wilkinson, Robert J and Coussens, Anna K and Esmail, Hanif},\r\ndoi = {10.1101/2024.06.30.24309731},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Macpherson et al. - 2024 - Diagnostic accuracy of Chest X-Ray Computer Aided Detection software and blood biomarkers for detection of pr.pdf:pdf},\r\njournal = {medRxiv},\r\nkeywords = {OA,fund{\\_}ack,original},\r\nmendeley-tags = {OA,fund{\\_}ack,original},\r\nmonth = {jul},\r\npages = {2024.06.30.24309731},\r\npublisher = {Cold Spring Harbor Laboratory Press},\r\ntitle = {{Diagnostic accuracy of chest X-Ray Computer Aided Detection software and blood biomarkers for detection of prevalent and incident tuberculosis in household contacts followed up for 5 years}},\r\nurl = {https://www.medrxiv.org/content/10.1101/2024.06.30.24309731v1 https://www.medrxiv.org/content/10.1101/2024.06.30.24309731v1.abstract},\r\nyear = {2024}\r\n}\r\n","author_short":["Macpherson, L.","Kik, S. V","Quartagno, M.","Lakay, F.","Jaftha, M.","Yende, N.","Galant, S.","Aziz, S.","Daroowala, R.","Court, R.","Taliep, A.","Serole, K.","Goliath, R. T","Davies, N. O.","Jackson, A.","Douglass, E.","Sossen, B.","Mukasa, S.","Thienemann, F.","Song, T.","Ruhwald, M.","Wilkinson, R. J","Coussens, A. K","Esmail, H."],"key":"Macpherson2024","id":"Macpherson2024","bibbaseid":"macpherson-kik-quartagno-lakay-jaftha-yende-galant-aziz-etal-diagnosticaccuracyofchestxraycomputeraideddetectionsoftwareandbloodbiomarkersfordetectionofprevalentandincidenttuberculosisinhouseholdcontactsfollowedupfor5years-2024","role":"author","urls":{"Paper":"https://www.medrxiv.org/content/10.1101/2024.06.30.24309731v1 https://www.medrxiv.org/content/10.1101/2024.06.30.24309731v1.abstract"},"keyword":["OA","fund_ack","original"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://drive.google.com/uc?export=download&id=1-JLqZ7RwZ3VC2d6ErLGHAtOeMRS_7GCz","dataSources":["Krmt6gt9ktB2s6ARh"],"keywords":["oa","fund_ack","original"],"search_terms":["diagnostic","accuracy","chest","ray","computer","aided","detection","software","blood","biomarkers","detection","prevalent","incident","tuberculosis","household","contacts","followed","years","macpherson","kik","quartagno","lakay","jaftha","yende","galant","aziz","daroowala","court","taliep","serole","goliath","davies","jackson","douglass","sossen","mukasa","thienemann","song","ruhwald","wilkinson","coussens","esmail"],"title":"Diagnostic accuracy of chest X-Ray Computer Aided Detection software and blood biomarkers for detection of prevalent and incident tuberculosis in household contacts followed up for 5 years","year":2024}