{
  "abstract": "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).",
  "authors": [
    {
      "affiliations": [
        "Swiss Tropical and Public Health Institute, Allschwil, Switzerland",
        "University of Basel, Basel, Switzerland"
      ],
      "name": "Aita Signorell"
    },
    {
      "affiliations": [
        "Centre for Community Based Research, Human Sciences Research Council, Sweetwaters, South Africa",
        "SAMRC/WITS Developmental Pathways for Health Research Unit, University of the Witwatersrand Johannesburg, Johannesburg, South Africa"
      ],
      "name": "Alastair van Heerden"
    },
    {
      "affiliations": [
        "SolidarMed, Butha Buthe, Lesotho"
      ],
      "name": "Irene Ayakaka"
    },
    {
      "affiliations": [
        "Institute of Tropical Medicine, Antwerpen, Belgium"
      ],
      "name": "Bart Karl Jacobs"
    },
    {
      "affiliations": [
        "Swiss Tropical and Public Health Institute, Allschwil, Switzerland",
        "University of Basel, Basel, Switzerland"
      ],
      "name": "Marina Antillon"
    },
    {
      "affiliations": [
        "Swiss Tropical and Public Health Institute, Allschwil, Switzerland",
        "University of Basel, Basel, Switzerland"
      ],
      "name": "Fabrizio Tediosi"
    },
    {
      "affiliations": [
        "Swiss Tropical and Public Health Institute, Allschwil, Switzerland",
        "University of Basel, Basel, Switzerland"
      ],
      "name": "Anna Verjans"
    },
    {
      "affiliations": [
        "Swiss Tropical and Public Health Institute, Allschwil, Switzerland",
        "University of Basel, Basel, Switzerland"
      ],
      "name": "Curdin Brugger"
    },
    {
      "affiliations": [
        "Swiss Tropical and Public Health Institute, Allschwil, Switzerland",
        "University of Basel, Basel, Switzerland"
      ],
      "name": "Harsh Vivek Harkare"
    },
    {
      "affiliations": [
        "Division of Clinical Epidemiology, Department of Clinical Research, University Hospital Basel, Basel, Switzerland",
        "University Hospital Basel, Basel, Switzerland"
      ],
      "name": "Niklaus Daniel Labhardt"
    },
    {
      "affiliations": [
        "Centre for Community Based Research, Human Sciences Research Council, Sweetwaters, South Africa"
      ],
      "name": "Shannon Bosman"
    },
    {
      "affiliations": [
        "SolidarMed, Butha Buthe, Lesotho"
      ],
      "name": "Mashaete Kamele"
    },
    {
      "affiliations": [
        "SolidarMed, Butha Buthe, Lesotho"
      ],
      "name": "Mamatlakeng Keitseng"
    },
    {
      "affiliations": [
        "Centre for Community Based Research, Human Sciences Research Council, Sweetwaters, South Africa"
      ],
      "name": "Thandanani Madonsela"
    },
    {
      "affiliations": [
        "Swiss Tropical and Public Health Institute, Allschwil, Switzerland",
        "University of Basel, Basel, Switzerland"
      ],
      "name": "Johanna Kurscheid"
    },
    {
      "affiliations": [
        "Partnerships for Health, USAID, Washington, District of Columbia, USA"
      ],
      "name": "Josephine Muhairwe"
    },
    {
      "affiliations": [
        "Center for International Health, Education, and Biosecurity, Nairobi, Kenya"
      ],
      "name": "Alfred Kipyegon Keter"
    },
    {
      "affiliations": [
        "Radboud University Medical Center, Nijmegen, The Netherlands"
      ],
      "name": "Keelin Murphy"
    },
    {
      "affiliations": [
        "Radboud University Medical Center, Nijmegen, The Netherlands"
      ],
      "name": "Bram van Ginneken"
    },
    {
      "affiliations": [
        "Institute of Tropical Medicine, Antwerpen, Belgium",
        "Global Health Institute, University of Antwerp, Wilrijk, Belgium"
      ],
      "name": "Tinne Gils"
    },
    {
      "affiliations": [
        "McGill University Health Centre, Montreal, Quebec, Canada"
      ],
      "name": "Bulemba Katende"
    },
    {
      "affiliations": [
        "BioInvent International AB, Lund, Sweden"
      ],
      "name": "Rediet Fikru Gebresenbet"
    },
    {
      "affiliations": [
        "Swiss Tropical and Public Health Institute, Allschwil, Switzerland",
        "University of Basel, Basel, Switzerland"
      ],
      "name": "Rahel Milena Erhardt"
    },
    {
      "affiliations": [
        "Department of Infectious Diseases and Respiratory Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany"
      ],
      "name": "Thomas Zoller"
    },
    {
      "affiliations": [
        "Swiss Tropical and Public Health Institute, Allschwil, Switzerland",
        "University of Basel, Basel, Switzerland"
      ],
      "name": "Fiona Vanobberghen"
    },
    {
      "affiliations": [
        "Swiss Tropical and Public Health Institute, Allschwil, Switzerland",
        "University of Basel, Basel, Switzerland"
      ],
      "name": "Tracy R Glass"
    },
    {
      "affiliations": [
        "Institute of Tropical Medicine, Antwerpen, Belgium"
      ],
      "name": "Lutgarde Lynen"
    },
    {
      "affiliations": [
        "Swiss Tropical and Public Health Institute, Allschwil, Switzerland",
        "University of Basel, Basel, Switzerland"
      ],
      "name": "Klaus Reither"
    }
  ],
  "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",
  "uid": "36149e21-ed0d-5026-9982-9b430413d312"
}