Effectiveness and cost-effectiveness of community-based TB screening algorithms using computer-aided detection (CAD) technology alone compared with CAD combined with point-of-care C reactive protein testing in Lesotho and South Africa: protocol for a paired screen-positive trial
Introduction Tuberculosis (TB) remains a significant public health challenge in many African communities, where underreporting and underdiagnosis are prevalent due to barriers in accessing care and inadequate diagnostic tools. This is particularly concerning in hard-to-reach areas with a high burden...
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2025-07-01
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| author | Fabrizio Tediosi Klaus Reither Bram van Ginneken Alastair van Heerden Tinne Gils Lutgarde Lynen Josephine Muhairwe Alfred Kipyegon Keter Aita Signorell Rediet Fikru Gebresenbet Irene Ayakaka Thomas Zoller Fiona Vanobberghen Mashaete Kamele Thandanani Madonsela Shannon Bosman Anna Verjans Bart Karl Jacobs Curdin Brugger Marina Antillon Niklaus Daniel Labhardt Harsh Vivek Harkare Mamatlakeng Keitseng Johanna Kurscheid Keelin Murphy Bulemba Katende Rahel Milena Erhardt Tracy R Glass |
| author_facet | Fabrizio Tediosi Klaus Reither Bram van Ginneken Alastair van Heerden Tinne Gils Lutgarde Lynen Josephine Muhairwe Alfred Kipyegon Keter Aita Signorell Rediet Fikru Gebresenbet Irene Ayakaka Thomas Zoller Fiona Vanobberghen Mashaete Kamele Thandanani Madonsela Shannon Bosman Anna Verjans Bart Karl Jacobs Curdin Brugger Marina Antillon Niklaus Daniel Labhardt Harsh Vivek Harkare Mamatlakeng Keitseng Johanna Kurscheid Keelin Murphy Bulemba Katende Rahel Milena Erhardt Tracy R Glass |
| author_sort | Fabrizio Tediosi |
| collection | DOAJ |
| description | Introduction Tuberculosis (TB) remains a significant public health challenge in many African communities, where underreporting and underdiagnosis are prevalent due to barriers in accessing care and inadequate diagnostic tools. This is particularly concerning in hard-to-reach areas with a high burden of TB/HIV co-infection, where missed or delayed diagnoses exacerbate disease transmission, increase mortality and lead to severe economic and health consequences. To address these challenges, it is crucial to evaluate innovative, cost-effective, community-based screening strategies that can improve early detection and linkage to care.Methods and analysis We conduct a prospective, community-based, diagnostic, pragmatic trial in communities of the Butha Buthe District in Lesotho and the Greater Edendale area of Msunduzi Municipality, KwaZulu-Natal in South Africa to compare two strategies for population-based TB screening: computer-aided detection (CAD) technology alone (CAD4TBv7 approach) versus CAD combined with point-of-care C reactive protein (CRP) testing (CAD4TBv7-CRP approach). Following a chest X-ray, CAD produces an abnormality score, which indicates the likelihood of TB. Score thresholds informing the screening logic for both approaches were determined based on the WHO’s target product profile for a TB screening test. CAD scores above a threshold prespecified for the CAD4TBv7 approach indicate confirmatory testing for TB (Xpert MTB/RIF Ultra). For the CAD4TBv7-CRP approach, a CAD score within a predefined window requires the conduct of the second screening test, CRP, while a score above the respective upper threshold is followed by Xpert MTB/RIF Ultra. A CRP result above the selected cut-off also requires a confirmatory TB test. Participants with CAD scores below the (lower) threshold and those with CRP levels below the cut-off are considered screen-negative. The trial aims to compare the yield of detected TB cases and cost-effectiveness between two screening approaches by applying a paired screen-positive design. 20 000 adult participants will be enrolled and will receive a posterior anterior digital chest X-ray which is analysed by CAD software.Ethics and dissemination The protocol was approved by National Health Research Ethics Committee in Lesotho (NH-REC, ID52-2022), the Human Sciences Research Council Research Ethics Committee (HSRC REC, REC 2/23/09/20) and the Provincial Health Research Committee of the Department of Health of KwaZulu-Natal (KZ_202209_022) in South Africa and from the Swiss Ethics Committee Northwest and Central Switzerland (EKNZ, AO_2022–00044). This manuscript is based on protocol V.4.0, 19 January 2024. Trial findings will be disseminated through peer-reviewed publications, conference presentations and through communication offices of the consortium partners and the project’s website (https://tbtriage.com/).Trial registration ClinicalTrials.gov (NCT05526885), South African National Clinical Trials Register (SANCTR; DOH-27-092022-8096). |
| format | Article |
| id | doaj-art-b8b92d960f7a4c83af99b00b38f01fba |
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| publishDate | 2025-07-01 |
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| spelling | doaj-art-b8b92d960f7a4c83af99b00b38f01fba2025-07-29T03:05:15ZengBMJ Publishing GroupBMJ Open2044-60552025-07-0115710.1136/bmjopen-2024-093989Effectiveness and cost-effectiveness of community-based TB screening algorithms using computer-aided detection (CAD) technology alone compared with CAD combined with point-of-care C reactive protein testing in Lesotho and South Africa: protocol for a paired screen-positive trialFabrizio Tediosi0Klaus Reither1Bram van Ginneken2Alastair van Heerden3Tinne Gils4Lutgarde Lynen5Josephine Muhairwe6Alfred Kipyegon Keter7Aita Signorell8Rediet Fikru Gebresenbet9Irene Ayakaka10Thomas Zoller11Fiona Vanobberghen12Mashaete Kamele13Thandanani Madonsela14Shannon Bosman15Anna Verjans16Bart Karl Jacobs17Curdin Brugger18Marina Antillon19Niklaus Daniel Labhardt20Harsh Vivek Harkare21Mamatlakeng Keitseng22Johanna Kurscheid23Keelin Murphy24Bulemba Katende25Rahel Milena Erhardt26Tracy R Glass27University of Basel, Basel, SwitzerlandUniversity of Basel, Basel, SwitzerlandRadboud University Medical Center, Nijmegen, The NetherlandsCentre for Community Based Research, Human Sciences Research Council, Sweetwaters, South AfricaInstitute of Tropical Medicine, Antwerpen, BelgiumInstitute of Tropical Medicine, Antwerpen, BelgiumPartnerships for Health, USAID, Washington, District of Columbia, USACenter for International Health, Education, and Biosecurity, Nairobi, KenyaSwiss Tropical and Public Health Institute, Allschwil, SwitzerlandBioInvent International AB, Lund, SwedenSolidarMed, Butha Buthe, LesothoDepartment of Infectious Diseases and Respiratory Medicine, Charité Universitätsmedizin Berlin, Berlin, GermanySwiss Tropical and Public Health Institute, Allschwil, SwitzerlandSolidarMed, Butha Buthe, LesothoCentre for Community Based Research, Human Sciences Research Council, Sweetwaters, South AfricaCentre for Community Based Research, Human Sciences Research Council, Sweetwaters, South AfricaSwiss Tropical and Public Health Institute, Allschwil, SwitzerlandInstitute of Tropical Medicine, Antwerpen, BelgiumSwiss Tropical and Public Health Institute, Allschwil, SwitzerlandSwiss Tropical and Public Health Institute, Allschwil, SwitzerlandDivision of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel, Basel, SwitzerlandSwiss Tropical and Public Health Institute, Allschwil, SwitzerlandSolidarMed, Butha Buthe, LesothoSwiss Tropical and Public Health Institute, Allschwil, SwitzerlandRadboud University Medical Center, Nijmegen, The NetherlandsMcGill University Health Centre, Montreal, Quebec, CanadaSwiss Tropical and Public Health Institute, Allschwil, SwitzerlandSwiss Tropical and Public Health Institute, Allschwil, SwitzerlandIntroduction Tuberculosis (TB) remains a significant public health challenge in many African communities, where underreporting and underdiagnosis are prevalent due to barriers in accessing care and inadequate diagnostic tools. This is particularly concerning in hard-to-reach areas with a high burden of TB/HIV co-infection, where missed or delayed diagnoses exacerbate disease transmission, increase mortality and lead to severe economic and health consequences. To address these challenges, it is crucial to evaluate innovative, cost-effective, community-based screening strategies that can improve early detection and linkage to care.Methods and analysis We conduct a prospective, community-based, diagnostic, pragmatic trial in communities of the Butha Buthe District in Lesotho and the Greater Edendale area of Msunduzi Municipality, KwaZulu-Natal in South Africa to compare two strategies for population-based TB screening: computer-aided detection (CAD) technology alone (CAD4TBv7 approach) versus CAD combined with point-of-care C reactive protein (CRP) testing (CAD4TBv7-CRP approach). Following a chest X-ray, CAD produces an abnormality score, which indicates the likelihood of TB. Score thresholds informing the screening logic for both approaches were determined based on the WHO’s target product profile for a TB screening test. CAD scores above a threshold prespecified for the CAD4TBv7 approach indicate confirmatory testing for TB (Xpert MTB/RIF Ultra). For the CAD4TBv7-CRP approach, a CAD score within a predefined window requires the conduct of the second screening test, CRP, while a score above the respective upper threshold is followed by Xpert MTB/RIF Ultra. A CRP result above the selected cut-off also requires a confirmatory TB test. Participants with CAD scores below the (lower) threshold and those with CRP levels below the cut-off are considered screen-negative. The trial aims to compare the yield of detected TB cases and cost-effectiveness between two screening approaches by applying a paired screen-positive design. 20 000 adult participants will be enrolled and will receive a posterior anterior digital chest X-ray which is analysed by CAD software.Ethics and dissemination The protocol was approved by National Health Research Ethics Committee in Lesotho (NH-REC, ID52-2022), the Human Sciences Research Council Research Ethics Committee (HSRC REC, REC 2/23/09/20) and the Provincial Health Research Committee of the Department of Health of KwaZulu-Natal (KZ_202209_022) in South Africa and from the Swiss Ethics Committee Northwest and Central Switzerland (EKNZ, AO_2022–00044). This manuscript is based on protocol V.4.0, 19 January 2024. Trial findings will be disseminated through peer-reviewed publications, conference presentations and through communication offices of the consortium partners and the project’s website (https://tbtriage.com/).Trial registration ClinicalTrials.gov (NCT05526885), South African National Clinical Trials Register (SANCTR; DOH-27-092022-8096).https://bmjopen.bmj.com/content/15/7/e093989.full |
| spellingShingle | Fabrizio Tediosi Klaus Reither Bram van Ginneken Alastair van Heerden Tinne Gils Lutgarde Lynen Josephine Muhairwe Alfred Kipyegon Keter Aita Signorell Rediet Fikru Gebresenbet Irene Ayakaka Thomas Zoller Fiona Vanobberghen Mashaete Kamele Thandanani Madonsela Shannon Bosman Anna Verjans Bart Karl Jacobs Curdin Brugger Marina Antillon Niklaus Daniel Labhardt Harsh Vivek Harkare Mamatlakeng Keitseng Johanna Kurscheid Keelin Murphy Bulemba Katende Rahel Milena Erhardt Tracy R Glass Effectiveness and cost-effectiveness of community-based TB screening algorithms using computer-aided detection (CAD) technology alone compared with CAD combined with point-of-care C reactive protein testing in Lesotho and South Africa: protocol for a paired screen-positive trial BMJ Open |
| title | Effectiveness and cost-effectiveness of community-based TB screening algorithms using computer-aided detection (CAD) technology alone compared with CAD combined with point-of-care C reactive protein testing in Lesotho and South Africa: protocol for a paired screen-positive trial |
| title_full | Effectiveness and cost-effectiveness of community-based TB screening algorithms using computer-aided detection (CAD) technology alone compared with CAD combined with point-of-care C reactive protein testing in Lesotho and South Africa: protocol for a paired screen-positive trial |
| title_fullStr | Effectiveness and cost-effectiveness of community-based TB screening algorithms using computer-aided detection (CAD) technology alone compared with CAD combined with point-of-care C reactive protein testing in Lesotho and South Africa: protocol for a paired screen-positive trial |
| title_full_unstemmed | Effectiveness and cost-effectiveness of community-based TB screening algorithms using computer-aided detection (CAD) technology alone compared with CAD combined with point-of-care C reactive protein testing in Lesotho and South Africa: protocol for a paired screen-positive trial |
| title_short | Effectiveness and cost-effectiveness of community-based TB screening algorithms using computer-aided detection (CAD) technology alone compared with CAD combined with point-of-care C reactive protein testing in Lesotho and South Africa: protocol for a paired screen-positive trial |
| title_sort | effectiveness and cost effectiveness of community based tb screening algorithms using computer aided detection cad technology alone compared with cad combined with point of care c reactive protein testing in lesotho and south africa protocol for a paired screen positive trial |
| url | https://bmjopen.bmj.com/content/15/7/e093989.full |
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