Blood transcriptomic signatures for symptomatic tuberculosis in an African multicohort study.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Corporate Authors:
      AE-TBC and ScreenTB Consortium
    • Source:
      Publisher: European Respiratory Society Country of Publication: England NLM ID: 8803460 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1399-3003 (Electronic) Linking ISSN: 09031936 NLM ISO Abbreviation: Eur Respir J Subsets: MEDLINE
    • Publication Information:
      Publication: Sheffield, United Kingdom : European Respiratory Society
      Original Publication: Copenhagen : Published jointly by the Society and Munksgaard, 1988-
    • Subject Terms:
      Transcriptome*; Humans ; Female ; Male ; Adult ; Case-Control Studies ; Middle Aged ; Gambia ; South Africa ; Ethiopia ; Malawi ; Uganda ; Tuberculosis, Pulmonary/blood ; Tuberculosis, Pulmonary/diagnosis ; Young Adult ; Mycobacterium tuberculosis/genetics ; Tuberculosis/blood ; Tuberculosis/diagnosis ; Tuberculosis/genetics ; Sensitivity and Specificity ; Namibia ; Sputum/microbiology ; Real-Time Polymerase Chain Reaction
    • Abstract:
      Background: Multiple host blood transcriptional signatures have been developed as non-sputum triage tests for tuberculosis (TB). We aimed to compare the diagnostic performance of 20 blood transcriptomic TB signatures for differentiating between symptomatic patients who have TB versus other respiratory diseases (ORD).
      Methods: As part of a nested case-control study, individuals presenting with respiratory symptoms at primary healthcare clinics in Ethiopia, Malawi, Namibia, Uganda, South Africa and The Gambia were enrolled. TB was diagnosed based on clinical, microbiological and radiological findings. Transcriptomic signatures were measured in whole blood using microfluidic real-time quantitative PCR. Diagnostic performance was benchmarked against the World Health Organization Target Product Profile (TPP) for a non-sputum TB triage test.
      Results: Among 579 participants, 158 had definite, microbiologically confirmed TB, 32 had probable TB, while 389 participants had ORD. Nine signatures differentiated between ORD and TB with equivalent performance (Satproedprai7: area under the curve 0.83 (95% CI 0.79-0.87); Jacobsen3: 0.83 (95% CI 0.79-0.86); Suliman2: 0.82 (95% CI 0.78-0.86); Roe1: 0.82 (95% CI 0.78-0.86); Kaforou22: 0.82 (95% CI 0.78-0.86); Sambarey10: 0.81 (95% CI 0.77-0.85); Duffy9: 0.81 (95% CI 0.76-0.86); Gliddon3: 0.8 (95% CI 0.75-0.85); Suliman4 0.79 (95% CI 0.75-0.84)). Benchmarked against a 90% sensitivity, these signatures achieved specificities between 44% (95% CI 38-49%) and 54% (95% CI 49-59%), not meeting the TPP criteria. Signature scores significantly varied by HIV status and country. In country-specific analyses, several signatures, such as Satproedprai7 and Penn-Nicholson6, met the minimal TPP criteria for a triage test in Ethiopia, Malawi and South Africa.
      Conclusion: No signatures met the TPP criteria in a pooled analysis of all countries, but several signatures met the minimum criteria for a non-sputum TB triage test in some countries.
      Competing Interests: Conflict of interest: G. Walzl and T.J. Scriba report grants from the Bill & Melinda Gates Foundation during the conduct of the study. T.J. Scriba and N.N. Chegou report grants from the South African Medical Research Council during the conduct of the study. G. Walzl reports grants from the South African National Research Foundation and EDCTP. T.J. Scriba has patents of the RISK11 (Darboe11), RISK6 (Penn-Nicholson6) and RISK4 (Suliman4) signatures issued. G. Walzl and N.N. Chegou have patents “TB diagnostic markers” (PCT/IB2013/054377), “Serum host biomarkers for tuberculosis disease” (PCT/IB2017/052142) and “Method for diagnosing TB” (PCT/IB2017/052142) granted but receive no royalties on these patents. The remaining authors have no potential conflicts of interest to disclose.
      (Copyright ©The authors 2024.)
    • Comments:
      Comment in: Eur Respir J. 2024 Aug 15;64(2):2401365. doi: 10.1183/13993003.01365-2024. (PMID: 39147423)
    • References:
      Thorax. 2016 Sep;71(9):785-94. (PMID: 27146200)
      Gates Open Res. 2023 Feb 3;7:27. (PMID: 37123047)
      Lancet Respir Med. 2020 Apr;8(4):407-419. (PMID: 32178775)
      EClinicalMedicine. 2022 Mar 05;45:101328. (PMID: 35274090)
      Front Immunol. 2018 Oct 23;9:2427. (PMID: 30405622)
      EBioMedicine. 2022 Aug;82:104174. (PMID: 35850011)
      Tuberculosis (Edinb). 2015 Jul;95(4):421-5. (PMID: 26025597)
      Front Immunol. 2021 May 19;12:664787. (PMID: 34093557)
      Genes Immun. 2015 Jun;16(4):253-60. (PMID: 25764116)
      Front Microbiol. 2019 Jun 26;10:1441. (PMID: 31297103)
      Commun Med (Lond). 2022;2(1):. (PMID: 35342900)
      Front Microbiol. 2016 Oct 25;7:1586. (PMID: 27826286)
      Lancet Infect Dis. 2021 Mar;21(3):354-365. (PMID: 33508224)
      PLoS Med. 2019 Apr 23;16(4):e1002786. (PMID: 31013272)
      Elife. 2021 Dec 23;10:. (PMID: 34939926)
      Lancet Respir Med. 2020 Apr;8(4):395-406. (PMID: 31958400)
      EBioMedicine. 2022 Apr;78:103928. (PMID: 35339424)
      Clin Infect Dis. 2020 Feb 14;70(5):731-737. (PMID: 30919880)
      J Clin Microbiol. 2021 Feb 18;59(3):. (PMID: 33298607)
      PLoS Med. 2013 Oct;10(10):e1001538. (PMID: 24167453)
      J Infect. 2019 Sep;79(3):228-235. (PMID: 31319143)
      Nat Microbiol. 2019 May;4(5):748-758. (PMID: 30804546)
      Respir Res. 2022 May 14;23(1):125. (PMID: 35568895)
      Nature. 2010 Aug 19;466(7309):973-7. (PMID: 20725040)
      Nat Commun. 2018 Jun 19;9(1):2308. (PMID: 29921861)
      Clin Infect Dis. 2019 Jun 18;69(1):77-83. (PMID: 30462176)
      JCI Insight. 2016 Oct 06;1(16):e87238. (PMID: 27734027)
      Am J Respir Crit Care Med. 2018 May 1;197(9):1198-1208. (PMID: 29624071)
      Front Immunol. 2021 Mar 02;12:637164. (PMID: 33763081)
      Nat Immunol. 2017 Aug 22;18(9):962-972. (PMID: 28829444)
      N Engl J Med. 2014 May 01;370(18):1712-1723. (PMID: 24785206)
      Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):E964-E973. (PMID: 29339504)
      Tuberculosis (Edinb). 2017 Dec;107:48-58. (PMID: 29050771)
      J Mol Med (Berl). 2007 Jun;85(6):613-21. (PMID: 17318616)
      PLoS One. 2019 Jul 15;14(7):e0219322. (PMID: 31306460)
      BMC Bioinformatics. 2011 Mar 17;12:77. (PMID: 21414208)
      EMBO Mol Med. 2022 Dec 7;14(12):e14088. (PMID: 36314872)
      EBioMedicine. 2022 Mar;77:103886. (PMID: 35183869)
      EMBO Mol Med. 2015 Dec 18;8(2):86-95. (PMID: 26682570)
      Lancet Infect Dis. 2021 Mar;21(3):366-375. (PMID: 33508221)
      Sci Rep. 2020 May 25;10(1):8629. (PMID: 32451443)
      PLoS One. 2014 Mar 19;9(3):e92340. (PMID: 24647646)
      J Infect. 2017 Dec;75(6):499-510. (PMID: 28941629)
      Clin Infect Dis. 2022 Jul 6;74(12):2136-2141. (PMID: 34550342)
      Front Microbiol. 2022 May 11;13:883513. (PMID: 35633669)
      Sci Rep. 2017 Jul 19;7(1):5839. (PMID: 28724962)
      PLoS One. 2013 Aug 05;8(8):e70630. (PMID: 23940611)
      Mol Immunol. 2020 Apr;120:187-195. (PMID: 32179338)
      Sci Rep. 2018 Feb 8;8(1):2675. (PMID: 29422548)
      Lancet Respir Med. 2016 Mar;4(3):213-24. (PMID: 26907218)
      PLoS One. 2020 Aug 21;15(8):e0237574. (PMID: 32822359)
      Biometrics. 1988 Sep;44(3):837-45. (PMID: 3203132)
      Nat Immunol. 2018 Nov;19(11):1159-1168. (PMID: 30333612)
      Cytokine Growth Factor Rev. 2018 Apr;40:19-31. (PMID: 29576284)
      EBioMedicine. 2017 Feb;15:112-126. (PMID: 28065665)
    • Publication Date:
      Date Created: 20240704 Date Completed: 20240815 Latest Revision: 20240817
    • Publication Date:
      20240817
    • Accession Number:
      PMC11325265
    • Accession Number:
      10.1183/13993003.00153-2024
    • Accession Number:
      38964778