{
  "abstract": "Introduction Since 2018, WHO has endorsed the use of whole-genome sequencing (WGS) of Mycobacterium tuberculosis complex isolates to detect drug-resistant tuberculosis (DR-TB). This endorsement was based on the assumption that a faster and more detailed description of the resistance profile would improve treatment prescription for DR-TB by healthcare providers, and hence the treatment outcomes of patients. Nonetheless, this assumption has not been tested in routine clinical practice and different scenarios. In Brazil, WGS is not routinely used for the diagnosis of DR-TB, having been carried out in only a few centres for research purposes. With this trial, we will evaluate whether a WGS-based drug-resistance report improves treatment adequacy in patients with pulmonary DR-TB, compared with the current standard-of-care diagnostic methods used in the state of São Paulo, Brazil.Methods and analysis We will conduct a non-randomised controlled clinical trial with two arms to compare the intervention group (ie, individuals receiving a WGS-based report) with a historical control group (i.e., individuals who received resistance diagnostics based on the standard of care of conventional genotyping and phenotyping techniques). The primary outcome will be the proportion of patients whose treatment scheme was adequate based on complete resistance profile determined by WGS and/or phenotypic drug-susceptibility testing (pDST). Other secondary outcomes will also be considered. The target sample size is 88 eligible patients per group. The intervention group will be prospectively recruited over 18 months and the control group will be composed of patients diagnosed with pulmonary DR-TB up to 2 years before the start of the trial. To ensure comparability, isolates from the control group will undergo WGS retrospectively, and pDST will be performed retrospectively in both groups. This clinical trial will take place in six medical centres for the treatment of DR-TB in the state of São Paulo. This study is intended to support the implementation of the WGS in the routine diagnosis of DR-TB in the state of São Paulo.Ethics and dissemination Ethical approval was obtained from the Human Research Committee of the Institute of Biomedical Sciences, University of São Paulo, Brazil (CAAE: 79497924.1.1001.5467). Study results will be published in peer-reviewed journals and disseminated to policymakers and stakeholders.Trial registration number U1111-1308-4669.",
  "authors": [
    {
      "affiliations": [
        "Department of Microbiology, University of São Paulo Institute of Biomedical Sciences, São Paulo, Brazil"
      ],
      "name": "Claudio Damião Rosa"
    },
    {
      "affiliations": [
        "Tuberculosis and Mycobacteriosis Laboratory (NTM), Adolfo Lutz Institute, São Paulo, Brazil"
      ],
      "name": "Lucilaine Ferrazoli"
    },
    {
      "affiliations": [
        "Tuberculosis and Mycobacteriosis Laboratory (NTM), Adolfo Lutz Institute, São Paulo, Brazil"
      ],
      "name": "Debora Pereira dos Santos"
    },
    {
      "affiliations": [
        "Tuberculosis and Mycobacteriosis Laboratory (NTM), Adolfo Lutz Institute, São Paulo, Brazil"
      ],
      "name": "Carolina Pedace"
    },
    {
      "affiliations": [
        "Department of Microbiology, University of São Paulo Institute of Biomedical Sciences, São Paulo, Brazil"
      ],
      "name": "Naila Cristina Soler-Camargo"
    },
    {
      "affiliations": [
        "Department of Microbiology, University of São Paulo Institute of Biomedical Sciences, São Paulo, Brazil"
      ],
      "name": "Taiana Tainá Silva-Pereira"
    },
    {
      "affiliations": [
        "Tuberculosis and Mycobacteriosis Laboratory (NTM), Adolfo Lutz Institute, São Paulo, Brazil",
        "Oswaldo Cruz Foundation, Rio de Janeiro, Brazil"
      ],
      "name": "Angela Pires Brandão"
    },
    {
      "affiliations": [
        "School of Medicine of Ribeirão Preto (FMRP), University of São Paulo, Ribeirão Preto, Brazil"
      ],
      "name": "Valdes Roberto Bollela"
    },
    {
      "affiliations": [
        "Health Economics Research Centre, University of Oxford, Oxford, UK"
      ],
      "name": "Ana Luíza Gibertoni Cruz"
    },
    {
      "affiliations": [
        "School of Medicine of Ribeirão Preto (FMRP), University of São Paulo, Ribeirão Preto, Brazil"
      ],
      "name": "Cinara Silva Feliciano"
    },
    {
      "affiliations": [
        "Division of Infectious Disease, School of Medicine, Federal University of São Paulo, Sao Paulo, Brazil"
      ],
      "name": "Paulo Roberto Abrão Ferreira"
    },
    {
      "affiliations": [
        "Division of Infectious Disease, School of Medicine, Federal University of São Paulo, Sao Paulo, Brazil"
      ],
      "name": "Erika Plascak Jorge"
    },
    {
      "affiliations": [
        "School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil"
      ],
      "name": "Silvana Spíndola de Miranda"
    },
    {
      "affiliations": [
        "Tuberculosis and Mycobacteriosis Laboratory (NTM), Adolfo Lutz Institute, São Paulo, Brazil"
      ],
      "name": "Rosangela Siqueira de Oliveira"
    },
    {
      "affiliations": [
        "Tuberculosis Division, Center for Epidemiologic Vigilance “Prof Alexandre Vranjac”, São Paulo State Secretariat of Health, São Paulo, Brazil"
      ],
      "name": "Maria de Lourdes Viude Oliveira"
    },
    {
      "affiliations": [
        "Tuberculosis Division, Center for Epidemiologic Vigilance “Prof Alexandre Vranjac”, São Paulo State Secretariat of Health, São Paulo, Brazil"
      ],
      "name": "Giovanna Mariah Orlandi"
    },
    {
      "affiliations": [
        "Tuberculosis and Mycobacteriosis Laboratory (NTM), Adolfo Lutz Institute, São Paulo, Brazil"
      ],
      "name": "Juliana Maira Watanabe Pinhata"
    },
    {
      "affiliations": [
        "Department of Clinical Medicine, School of Medical Sciences, State University of Campinas, Campinas, Brazil"
      ],
      "name": "Mariângela Ribeiro Resende"
    },
    {
      "affiliations": [
        "Emilio Ribas Institute of Infectious Diseases, São Paulo, Brazil"
      ],
      "name": "Camila Rodrigues"
    },
    {
      "affiliations": [
        "Department of Pneumology, School of Medicine, University of São Paulo, São Paulo, Brazil"
      ],
      "name": "Roberta Karla Barbosa de Sales"
    },
    {
      "affiliations": [
        "Reference and Training Center on Sexually Transmitted Infections and AIDS (CRT-IST/AIDS) of the State of São Paulo, São Paulo, Brazil"
      ],
      "name": "Sumire Sakabe"
    },
    {
      "affiliations": [
        "Tuberculosis and Mycobacteriosis Laboratory (NTM), Adolfo Lutz Institute, São Paulo, Brazil"
      ],
      "name": "Erica Chimara"
    },
    {
      "affiliations": [
        "Department of Microbiology, University of São Paulo Institute of Biomedical Sciences, São Paulo, Brazil"
      ],
      "name": "Ana Marcia Sa Guimaraes"
    }
  ],
  "title": "Impact of drug-resistance diagnosis based on whole-genome sequencing on the treatment adequacy of patients with drug-resistant pulmonary tuberculosis in the state of São Paulo, Brazil: a protocol for a non-randomised controlled trial (Gen-TB PróCura)",
  "uid": "2b85ea8b-b2cc-5eae-9d4e-465979944641"
}