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

 

Show simple item record

dc.contributor.author Kaforou, Myrsini en_ZA
dc.contributor.author Wright, Victoria J en_ZA
dc.contributor.author Oni, Tolu en_ZA
dc.contributor.author French, Neil en_ZA
dc.contributor.author Anderson, Suzanne T en_ZA
dc.contributor.author Bangani, Nonzwakazi en_ZA
dc.contributor.author Banwell, Claire M en_ZA
dc.contributor.author Brent, Andrew J en_ZA
dc.contributor.author Crampin, Amelia C en_ZA
dc.contributor.author Dockrell, Hazel M en_ZA
dc.date.accessioned 2015-12-28T06:47:24Z
dc.date.available 2015-12-28T06:47:24Z
dc.date.issued 2013 en_ZA
dc.identifier.citation Kaforou, 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.1001538 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/16025
dc.identifier.uri http://dx.doi.org/10.1371/journal.pmed.1001538
dc.description.abstract 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. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This 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.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLOS Medicince en_ZA
dc.source.uri http://journals.plos.org/plosmedicine en_ZA
dc.subject.other Tuberculosis en_ZA
dc.subject.other Tuberculosis diagnosis and management en_ZA
dc.subject.other Diagnostic medicine en_ZA
dc.subject.other HIV en_ZA
dc.subject.other HIV diagnosis and management en_ZA
dc.subject.other Blood en_ZA
dc.subject.other Malawi en_ZA
dc.subject.other Mycobacterium tuberculosis en_ZA
dc.title Detection of tuberculosis in HIV-infected and-uninfected African adults using whole blood RNA expression signatures: a case-control study en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2013 Kaforou et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Institute of Infectious Disease and Molecular Medicine en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Kaforou, 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/11427/16025 en_ZA
dc.identifier.chicagocitation Kaforou, 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/11427/16025 en_ZA
dc.identifier.vancouvercitation Kaforou 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.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


Files in this item

This item appears in the following Collection(s)

Show simple item record

This 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. Except where otherwise noted, this item's license is described as This 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.