{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:58:06Z","timestamp":1781719086079,"version":"3.54.5"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001713","name":"EDCTP","doi-asserted-by":"crossref","award":["TMA2019SFP-2836 TB lung-FACT2"],"award-info":[{"award-number":["TMA2019SFP-2836 TB lung-FACT2"]}],"id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000061","name":"Fogarty International Center","doi-asserted-by":"publisher","award":["K43TW011028"],"award-info":[{"award-number":["K43TW011028"]}],"id":[{"id":"10.13039\/100000061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001322","name":"South African Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"South African National Research Foundation","award":["SARCHI: Chair in Paediatric Tuberculosis"],"award-info":[{"award-number":["SARCHI: Chair in Paediatric Tuberculosis"]}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00004\/04"],"award-info":[{"award-number":["MC_UU_00004\/04"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_00004\/04"],"award-info":[{"award-number":["MC_UU_00004\/04"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosglobalpublichealth.org"],"crossmark-restriction":false},"short-container-title":["PLOS Glob Public Health"],"abstract":"<jats:p>Implementation of the World Health Organization\u2019s (WHO) recommended shorter 4-month treatment regimen for non-severe tuberculosis (TB) in children requires classification of disease severity on chest X-ray (CXR). Access to specialists for CXR interpretation is limited. We explored the use of computer-aided detection of CXR (\u201cCAD\u201d) to automate CXR classification of radiological disease severity. To do this, we combined three CXR datasets from children with confirmed and clinically diagnosed TB across the disease spectrum. CXRs were independently classified as radiologically severe or non-severe by two expert human readers. Definition of radiological disease severity aligned with WHO guidelines. CAD scores were generated by CAD4TB v7.0 and qXR v3.0 software. Neither software product was specifically trained with paediatric CXRs or for disease severity classification. We compared CAD scores between CXRs classified by human readers as non-severe versus CXRs classified by human readers as severe. CXRs from 526 children were included in this analysis: median age was 2.1 years (inter-quartile range 1-4.2 years); 57% of the children had microbiologically confirmed TB. We found that median CAD scores were significantly lower for CXRs classified as non-severe versus severe by human readers; the difference was greatest in children &gt;5 years. The area under the receiver operating curve was 0.82 and 0.78 for qXR, and 0.79 and 0.76 for CAD4TB, against the reference of \u2018severe\u2019 as classified by each individual human reader respectively. These results demonstrate that CAD is a promising tool for TB disease severity stratification and has the potential to support access to shorter TB treatment regimens for children. Investment in paediatric CAD training and development to optimize solutions for children beyond the TB screening and diagnosis use-case is warranted.<\/jats:p>","DOI":"10.1371\/journal.pgph.0006547","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:34:51Z","timestamp":1781717691000},"page":"e0006547","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgph.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Computer-aided detection for radiological disease severity classification on chest radiograph in children with intra-thoracic tuberculosis"],"prefix":"10.1371","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2534-2483","authenticated-orcid":true,"given":"Megan","family":"Palmer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7070-5036","authenticated-orcid":true,"given":"Ineke","family":"Derks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5755-4133","authenticated-orcid":true,"given":"H. Simon","family":"Schaaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Goussard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devan","family":"Jaganath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra V.","family":"Kik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana M.","family":"Gibb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Turkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Walters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8787-9139","authenticated-orcid":true,"given":"Marieke M.","family":"van der Zalm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke C.","family":"Hesseling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2296-2302","authenticated-orcid":true,"given":"James A.","family":"Seddon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"pgph.0006547.ref001","unstructured":"World Health Organization. Global Tuberculosis Report. 2024. Available at: Global Tuberculosis Report 2024. 2025."},{"key":"pgph.0006547.ref002","unstructured":"United Nations. Political Declaration on the High-Level Meeting on the Fight Against Tuberculosis \u201cAdvancing science, finance and innovation, and their benefits, to urgently end the global tuberculosis epidemic, in particular by ensuring equitable access to prevention, testing, treatment and care\u201d. Political Declaration of the High-Level Meeting on the Fight Against Tuberculosis. 2023."},{"issue":"6","key":"pgph.0006547.ref003","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1038\/s41591-025-03742-3","article-title":"Strategies for shortening tuberculosis therapy","volume":"31","author":"VA Dartois","year":"2025","journal-title":"Nat Med"},{"key":"pgph.0006547.ref004","author":"World Health Organization","year":"2023"},{"issue":"12","key":"pgph.0006547.ref005","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgph.0001337","article-title":"Cost-effectiveness of short, oral treatment regimens for rifampicin resistant tuberculosis","volume":"2","author":"S Sweeney","year":"2022","journal-title":"PLOS Glob Public Health"},{"issue":"10","key":"pgph.0006547.ref006","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1056\/NEJMoa2104535","article-title":"Shorter Treatment for Nonsevere Tuberculosis in African and Indian Children","volume":"386","author":"A Turkova","year":"2022","journal-title":"N Engl J Med"},{"issue":"3","key":"pgph.0006547.ref007","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2024-088556","article-title":"Patients\u2019 acceptability, adherence and satisfaction on the modified shorter all-oral multidrug-resistant tuberculosis regimen: a two-phase cross-sectional study in Tanzania","volume":"15","author":"J Lalashowi","year":"2025","journal-title":"BMJ Open"},{"issue":"18","key":"pgph.0006547.ref008","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1056\/NEJMoa2033400","article-title":"Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis","volume":"384","author":"SE Dorman","year":"2021","journal-title":"N Engl J Med"},{"key":"pgph.0006547.ref009","unstructured":"World Health Organization. WHO consolidated guidelines on tuberculosis. Module 5: Management of tuberculosis in children and adolescents. 2022."},{"issue":"1","key":"pgph.0006547.ref010","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1186\/s13063-018-2608-5","article-title":"Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial","volume":"19","author":"C Chabala","year":"2018","journal-title":"Trials"},{"key":"pgph.0006547.ref011","unstructured":"World Health Organization. Child and adolscent working group meeting. Bali:The union; 2024."},{"issue":"9","key":"pgph.0006547.ref012","first-page":"814","article-title":"Observer variation in detecting lymphadenopathy on chest radiography","volume":"6","author":"G Du Toit","year":"2002","journal-title":"Int J Tuberc Lung Dis"},{"issue":"8","key":"pgph.0006547.ref013","doi-asserted-by":"crossref","first-page":"844","DOI":"10.5588\/ijtld.18.0122","article-title":"Value of chest X-ray in TB diagnosis in HIV-infected children living in resource-limited countries: the ANRS 12229-PAANTHER 01 study","volume":"22","author":"L Berteloot","year":"2018","journal-title":"Int J Tuberc Lung Dis"},{"key":"pgph.0006547.ref014","doi-asserted-by":"crossref","first-page":"291841","DOI":"10.1155\/2014\/291841","article-title":"Chest Radiographs for Pediatric TB Diagnosis: Interrater Agreement and Utility","volume":"2014","author":"G Kaguthi","year":"2014","journal-title":"Interdiscip Perspect Infect Dis"},{"issue":"3","key":"pgph.0006547.ref015","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1590\/S1516-31802007000300005","article-title":"Inter-observer agreement in interpreting chest X-rays on children with acute lower respiratory tract infections and concurrent wheezing","volume":"125","author":"C Bada","year":"2007","journal-title":"Sao Paulo Med J"},{"issue":"8","key":"pgph.0006547.ref016","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.1002\/ppul.25528","article-title":"Interobserver agreement in interpretation of chest radiographs for pediatric community acquired pneumonia: Findings of the pedCAPNETZ-cohort","volume":"56","author":"GM Voigt","year":"2021","journal-title":"Pediatr Pulmonol"},{"issue":"3","key":"pgph.0006547.ref017","first-page":"147","article-title":"Interobserver Agreement in Assessment of Chest Radiographs for the Diagnosis of Pneumonia between Residents and Radiologists in a Pediatric Emergency Department: The Role of patient and Resident Characteristics","volume":"27","author":"T Pelts-Shlayer","year":"2025","journal-title":"Isr Med Assoc J"},{"issue":"12","key":"pgph.0006547.ref018","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1002\/ppul.22806","article-title":"Variability and accuracy in interpretation of consolidation on chest radiography for diagnosing pneumonia in children under 5 years of age","volume":"48","author":"GJ Williams","year":"2013","journal-title":"Pediatr Pulmonol"},{"issue":"6","key":"pgph.0006547.ref019","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1093\/cid\/ciac011","article-title":"The diagnostic accuracy of chest radiographic features for pediatric intrathoracic tuberculosis","volume":"75","author":"M Palmer","year":"2022","journal-title":"Clin Infect Dis"},{"issue":"2","key":"pgph.0006547.ref020","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.crad.2020.08.035","article-title":"Reliability of chest radiograph interpretation for pulmonary 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computer-aided detection (CAD) software and radiologists from multiple countries for tuberculosis detection in chest X-Rays","volume":"15","author":"ZZ Qin","year":"2025","journal-title":"Sci Rep"},{"issue":"1","key":"pgph.0006547.ref024","doi-asserted-by":"crossref","first-page":"23895","DOI":"10.1038\/s41598-021-03265-0","article-title":"Independent evaluation of 12 artificial intelligence solutions for the detection of tuberculosis","volume":"11","author":"AJ Codlin","year":"2021","journal-title":"Sci Rep"},{"issue":"9","key":"pgph.0006547.ref025","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1097\/INF.0000000000001563","article-title":"Xpert MTB\/RIF on Stool Is Useful for the Rapid Diagnosis of Tuberculosis in Young Children With Severe Pulmonary Disease","volume":"36","author":"E Walters","year":"2017","journal-title":"Pediatr Infect Dis J"},{"key":"pgph.0006547.ref026","doi-asserted-by":"crossref","DOI":"10.1093\/cid\/civ581","article-title":"Clinical case definitions for classification of intrathoracic tuberculosis in children: an update","volume":"61","author":"SM Graham","year":"2015","journal-title":"Clin Infect Dis"},{"issue":"7","key":"pgph.0006547.ref027","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1097\/INF.0000000000002631","article-title":"Trends in Drug Resistance in Childhood Tuberculosis in Cape Town, South Africa","volume":"39","author":"HS Schaaf","year":"2020","journal-title":"Pediatr Infect Dis J"},{"issue":"11","key":"pgph.0006547.ref028","doi-asserted-by":"crossref","first-page":"547","DOI":"10.5588\/ijtld.24.0076","article-title":"Approaches and processes for paediatric chest X-ray classification used in the SHINE TB treatment-shortening trial","volume":"28","author":"M Palmer","year":"2024","journal-title":"Int J Tuberc Lung Dis"},{"key":"pgph.0006547.ref029","unstructured":"29.R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing. 2024."},{"issue":"1","key":"pgph.0006547.ref030","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1177\/001316446002000104","article-title":"A Coefficient of Agreement for Nominal Scales","volume":"20","author":"J Cohen","year":"1960","journal-title":"Educational and Psychological Measurement"},{"issue":"1","key":"pgph.0006547.ref031","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2307\/2529310","article-title":"The measurement of observer agreement for categorical data","volume":"33","author":"JR Landis","year":"1977","journal-title":"Biometrics"},{"issue":"268","key":"pgph.0006547.ref032","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1080\/01621459.1954.10501232","article-title":"A Test of Goodness of Fit","volume":"49","author":"TW Anderson","year":"1954","journal-title":"J Am Statistical Association"},{"issue":"1","key":"pgph.0006547.ref033","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1214\/aoms\/1177730491","article-title":"On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other","volume":"18","author":"HB Mann","year":"1947","journal-title":"Ann Math Statist"},{"issue":"1","key":"pgph.0006547.ref034","doi-asserted-by":"crossref","first-page":"12380","DOI":"10.1038\/s41598-024-60861-6","article-title":"A multistage framework for respiratory disease detection and assessing severity in chest X-ray images","volume":"14","author":"P Sahoo","year":"2024","journal-title":"Sci Rep"},{"key":"pgph.0006547.ref035","doi-asserted-by":"crossref","first-page":"106947","DOI":"10.1016\/j.cmpb.2022.106947","article-title":"Disease Localization and Severity Assessment in Chest X-Ray Images using Multi-Stage Superpixels Classification","volume":"222","author":"TB Chandra","year":"2022","journal-title":"Comput Methods Programs Biomed"},{"issue":"7","key":"pgph.0006547.ref036","article-title":"Predicting COVID-19 Pneumonia Severity on Chest X-ray With Deep Learning","volume":"12","author":"JP Cohen","year":"2020","journal-title":"Cureus"},{"issue":"5","key":"pgph.0006547.ref037","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1007\/s10278-024-01052-7","article-title":"Automated pulmonary tuberculosis severity assessment on chest x-rays","volume":"37","author":"K Kantipudi","year":"2024","journal-title":"J Imaging Inform Med"}],"container-title":["PLOS Global Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgph.0006547","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:34:59Z","timestamp":1781717699000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgph.0006547"}},"subtitle":[],"editor":[{"given":"Priya","family":"Rajendran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,17]]},"references-count":37,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgph.0006547","relation":{},"ISSN":["2767-3375"],"issn-type":[{"value":"2767-3375","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,17]]}}}