Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pmed.1001538
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dc.titleDetection of Tuberculosis in HIV-Infected and -Uninfected African Adults Using Whole Blood RNA Expression Signatures: A Case-Control Study
dc.contributor.authorKaforou M.
dc.contributor.authorWright V.J.
dc.contributor.authorOni T.
dc.contributor.authorFrench N.
dc.contributor.authorAnderson S.T.
dc.contributor.authorBangani N.
dc.contributor.authorBanwell C.M.
dc.contributor.authorBrent A.J.
dc.contributor.authorCrampin A.C.
dc.contributor.authorDockrell H.M.
dc.contributor.authorEley B.
dc.contributor.authorHeyderman R.S.
dc.contributor.authorHibberd M.L.
dc.contributor.authorKern F.
dc.contributor.authorLangford P.R.
dc.contributor.authorLing L.
dc.contributor.authorMendelson M.
dc.contributor.authorOttenhoff T.H.
dc.contributor.authorZgambo F.
dc.contributor.authorWilkinson R.J.
dc.contributor.authorCoin L.J.
dc.contributor.authorLevin M.
dc.date.accessioned2019-11-06T09:25:28Z
dc.date.available2019-11-06T09:25:28Z
dc.date.issued2013
dc.identifier.citationKaforou M., Wright V.J., Oni T., French N., Anderson S.T., Bangani N., Banwell C.M., Brent A.J., Crampin A.C., Dockrell H.M., Eley B., Heyderman R.S., Hibberd M.L., Kern F., Langford P.R., Ling L., Mendelson M., Ottenhoff T.H., Zgambo F., Wilkinson R.J., Coin L.J., Levin M. (2013). Detection of Tuberculosis in HIV-Infected and -Uninfected African Adults Using Whole Blood RNA Expression Signatures: A Case-Control Study. PLoS Medicine 10 (10) : e1001538. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pmed.1001538
dc.identifier.issn15491277
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/161616
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.Please see later in the article for the Editors' Summary. © 2013 Kaforou et al.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20191101
dc.subjectadult
dc.subjectarea under the curve
dc.subjectarticle
dc.subjectcase control study
dc.subjectcluster analysis
dc.subjectcontrolled study
dc.subjectfemale
dc.subjectfollow up
dc.subjectgene expression
dc.subjectgeographic distribution
dc.subjecthuman
dc.subjectHuman immunodeficiency virus infected patient
dc.subjecthuman tissue
dc.subjectmajor clinical study
dc.subjectMalawi
dc.subjectmale
dc.subjectmicroarray analysis
dc.subjectnucleotide sequence
dc.subjectperformance
dc.subjectprevalence
dc.subjectrisk factor
dc.subjectscoring system
dc.subjectsensitivity and specificity
dc.subjectSouth Africa
dc.subjectsputum analysis
dc.subjecttuberculosis
dc.subjectvalidation process
dc.subjectAdult
dc.subjectAfrica
dc.subjectCase-Control Studies
dc.subjectHIV Infections
dc.subjectHumans
dc.subjectRNA
dc.subjectTuberculosis
dc.typeArticle
dc.contributor.departmentSAW SWEE HOCK SCHOOL OF PUBLIC HEALTH
dc.description.doi10.1371/journal.pmed.1001538
dc.description.sourcetitlePLoS Medicine
dc.description.volume10
dc.description.issue10
dc.description.pagee1001538
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