Detection of tuberculosis in HIV-infected and-uninfected African adults using whole blood RNA expression signatures: a case-control study

Simple item page
dc.contributor.authorKaforou, Myrsinien_ZA
dc.contributor.authorWright, Victoria Jen_ZA
dc.contributor.authorOni, Toluen_ZA
dc.contributor.authorFrench, Neilen_ZA
dc.contributor.authorAnderson, Suzanne Ten_ZA
dc.contributor.authorBangani, Nonzwakazien_ZA
dc.contributor.authorBanwell, Claire Men_ZA
dc.contributor.authorBrent, Andrew Jen_ZA
dc.contributor.authorCrampin, Amelia Cen_ZA
dc.contributor.authorDockrell, Hazel Men_ZA
dc.date.accessioned2015-12-28T06:47:24Z
dc.date.available2015-12-28T06:47:24Z
dc.date.issued2013en_ZA
dc.description.abstractBackground: A major impediment to tuberculosis control in Africa is the difficulty in diagnosing active tuberculosis (TB), particularly in the context of HIV infection. We hypothesized that a unique host blood RNA transcriptional signature would distinguish TB from other diseases (OD) in HIV-infected and -uninfected patients, and that this could be the basis of a simple diagnostic test. Methods and Findings: Adult case-control cohorts were established in South Africa and Malawi of HIV-infected or -uninfected individuals consisting of 584 patients with either TB (confirmed by culture of Mycobacterium tuberculosis [M.TB] from sputum or tissue sample in a patient under investigation for TB), OD (i.e., TB was considered in the differential diagnosis but then excluded), or healthy individuals with latent TB infection (LTBI). Individuals were randomized into training (80%) and test (20%) cohorts. Blood transcriptional profiles were assessed and minimal sets of significantly differentially expressed transcripts distinguishing TB from LTBI and OD were identified in the training cohort. A 27 transcript signature distinguished TB from LTBI and a 44 transcript signature distinguished TB from OD. To evaluate our signatures, we used a novel computational method to calculate a disease risk score (DRS) for each patient. The classification based on this score was first evaluated in the test cohort, and then validated in an independent publically available dataset (GSE19491). In our test cohort, the DRS classified TB from LTBI (sensitivity 95%, 95% CI [87–100]; specificity 90%, 95% CI [80–97]) and TB from OD (sensitivity 93%, 95% CI [83–100]; specificity 88%, 95% CI [74–97]). In the independent validation cohort, TB patients were distinguished both from LTBI individuals (sensitivity 95%, 95% CI [85–100]; specificity 94%, 95% CI [84–100]) and OD patients (sensitivity 100%, 95% CI [100–100]; specificity 96%, 95% CI [93–100]). Limitations of our study include the use of only culture confirmed TB patients, and the potential that TB may have been misdiagnosed in a small proportion of OD patients despite the extensive clinical investigation used to assign each patient to their diagnostic group. Conclusions: In our study, blood transcriptional signatures distinguished TB from other conditions prevalent in HIV-infected and -uninfected African adults. Our DRS, based on these signatures, could be developed as a test for TB suitable for use in HIV endemic countries. Further evaluation of the performance of the signatures and DRS in prospective populations of patients with symptoms consistent with TB will be needed to define their clinical value under operational conditions.en_ZA
dc.identifier.apacitationKaforou, M., Wright, V. J., Oni, T., French, N., Anderson, S. T., Bangani, N., ... Dockrell, H. M. (2013). Detection of tuberculosis in HIV-infected and-uninfected African adults using whole blood RNA expression signatures: a case-control study. <i>PLOS Medicince</i>, http://hdl.handle.net/11427/16025en_ZA
dc.identifier.chicagocitationKaforou, Myrsini, Victoria J Wright, Tolu Oni, Neil French, Suzanne T Anderson, Nonzwakazi Bangani, Claire M Banwell, Andrew J Brent, Amelia C Crampin, and Hazel M Dockrell "Detection of tuberculosis in HIV-infected and-uninfected African adults using whole blood RNA expression signatures: a case-control study." <i>PLOS Medicince</i> (2013) http://hdl.handle.net/11427/16025en_ZA
dc.identifier.citationKaforou, M., Wright, V. J., Oni, T., French, N., Anderson, S. T., Bangani, N., ... & Eley, B. (2013). Detection of tuberculosis in HIV-infected and-uninfected African adults using whole blood RNA expression signatures: a case-control study. PLoS Med, 10(10), e1001538. doi:10.1371/journal.pmed.1001538en_ZA
dc.identifier.ris TY - Journal Article AU - Kaforou, Myrsini AU - Wright, Victoria J AU - Oni, Tolu AU - French, Neil AU - Anderson, Suzanne T AU - Bangani, Nonzwakazi AU - Banwell, Claire M AU - Brent, Andrew J AU - Crampin, Amelia C AU - Dockrell, Hazel M AB - Background: A major impediment to tuberculosis control in Africa is the difficulty in diagnosing active tuberculosis (TB), particularly in the context of HIV infection. We hypothesized that a unique host blood RNA transcriptional signature would distinguish TB from other diseases (OD) in HIV-infected and -uninfected patients, and that this could be the basis of a simple diagnostic test. Methods and Findings: Adult case-control cohorts were established in South Africa and Malawi of HIV-infected or -uninfected individuals consisting of 584 patients with either TB (confirmed by culture of Mycobacterium tuberculosis [M.TB] from sputum or tissue sample in a patient under investigation for TB), OD (i.e., TB was considered in the differential diagnosis but then excluded), or healthy individuals with latent TB infection (LTBI). Individuals were randomized into training (80%) and test (20%) cohorts. Blood transcriptional profiles were assessed and minimal sets of significantly differentially expressed transcripts distinguishing TB from LTBI and OD were identified in the training cohort. A 27 transcript signature distinguished TB from LTBI and a 44 transcript signature distinguished TB from OD. To evaluate our signatures, we used a novel computational method to calculate a disease risk score (DRS) for each patient. The classification based on this score was first evaluated in the test cohort, and then validated in an independent publically available dataset (GSE19491). In our test cohort, the DRS classified TB from LTBI (sensitivity 95%, 95% CI [87–100]; specificity 90%, 95% CI [80–97]) and TB from OD (sensitivity 93%, 95% CI [83–100]; specificity 88%, 95% CI [74–97]). In the independent validation cohort, TB patients were distinguished both from LTBI individuals (sensitivity 95%, 95% CI [85–100]; specificity 94%, 95% CI [84–100]) and OD patients (sensitivity 100%, 95% CI [100–100]; specificity 96%, 95% CI [93–100]). Limitations of our study include the use of only culture confirmed TB patients, and the potential that TB may have been misdiagnosed in a small proportion of OD patients despite the extensive clinical investigation used to assign each patient to their diagnostic group. Conclusions: In our study, blood transcriptional signatures distinguished TB from other conditions prevalent in HIV-infected and -uninfected African adults. Our DRS, based on these signatures, could be developed as a test for TB suitable for use in HIV endemic countries. Further evaluation of the performance of the signatures and DRS in prospective populations of patients with symptoms consistent with TB will be needed to define their clinical value under operational conditions. DA - 2013 DB - OpenUCT DO - 10.1371/journal.pmed.1001538 DP - University of Cape Town J1 - PLOS Medicince LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - Detection of tuberculosis in HIV-infected and-uninfected African adults using whole blood RNA expression signatures: a case-control study TI - Detection of tuberculosis in HIV-infected and-uninfected African adults using whole blood RNA expression signatures: a case-control study UR - http://hdl.handle.net/11427/16025 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16025
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pmed.1001538
dc.identifier.vancouvercitationKaforou M, Wright VJ, Oni T, French N, Anderson ST, Bangani N, et al. Detection of tuberculosis in HIV-infected and-uninfected African adults using whole blood RNA expression signatures: a case-control study. PLOS Medicince. 2013; http://hdl.handle.net/11427/16025.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2013 Kaforou et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLOS Medicinceen_ZA
dc.source.urihttp://journals.plos.org/plosmedicineen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherTuberculosis diagnosis and managementen_ZA
dc.subject.otherDiagnostic medicineen_ZA
dc.subject.otherHIVen_ZA
dc.subject.otherHIV diagnosis and managementen_ZA
dc.subject.otherBlooden_ZA
dc.subject.otherMalawien_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.titleDetection of tuberculosis in HIV-infected and-uninfected African adults using whole blood RNA expression signatures: a case-control studyen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Kaforou_Detection_of_Tuberculosis_in_HIV_2013.pdf
Size:
1.37 MB
Format:
Adobe Portable Document Format
Description:
Download
Collections
Journal Articles