Diagnosis of childhood tuberculosis and host RNA expression in Africa

Anderson, Suzanne T., Kaforou, Myrsini, Brent, Andrew J., Wright, Victoria J., Banwell, Claire M., Chagaluka, George, Crampin, Amelia C., Dockrell, Hazel M., French, Neil, Hamilton, Melissa S., Hibberd, Martin L., Kern, Florian, Langford, Paul R., Ling, Ling, Mlotha, Rachel, Ottenhoff, Tom H. M., Pienaar, Sandy, Pillay, Vashini, Scott, J. Anthony G., Twahir, Hemed, Wilkinson, Robert J., Coin, Lachlan J., Heyderman, Robert S., Levin, Michael, Eley, Brian and for the ILULU Consortium and KIDS TB Study Group (2014) Diagnosis of childhood tuberculosis and host RNA expression in Africa. New England Journal of Medicine, 370 18: 1712-1723. doi:10.1056/NEJMoa1303657

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Author Anderson, Suzanne T.
Kaforou, Myrsini
Brent, Andrew J.
Wright, Victoria J.
Banwell, Claire M.
Chagaluka, George
Crampin, Amelia C.
Dockrell, Hazel M.
French, Neil
Hamilton, Melissa S.
Hibberd, Martin L.
Kern, Florian
Langford, Paul R.
Ling, Ling
Mlotha, Rachel
Ottenhoff, Tom H. M.
Pienaar, Sandy
Pillay, Vashini
Scott, J. Anthony G.
Twahir, Hemed
Wilkinson, Robert J.
Coin, Lachlan J.
Heyderman, Robert S.
Levin, Michael
Eley, Brian
for the ILULU Consortium and KIDS TB Study Group
Title Diagnosis of childhood tuberculosis and host RNA expression in Africa
Journal name New England Journal of Medicine   Check publisher's open access policy
ISSN 1533-4406
Publication date 2014-05-01
Year available 2014
Sub-type Article (original research)
DOI 10.1056/NEJMoa1303657
Open Access Status File (Publisher version)
Volume 370
Issue 18
Start page 1712
End page 1723
Total pages 12
Place of publication Waltham, MA United States
Publisher Massachussetts Medical Society
Language eng
Formatted abstract
BACKGROUND: Improved diagnostic tests for tuberculosis in children are needed. We hypothesized that transcriptional signatures of host blood could be used to distinguish tuberculosis from other diseases in African children who either were or were not infected with the human immunodeficiency virus (HIV).

METHODS: The study population comprised prospective cohorts of children who were undergoing evaluation for suspected tuberculosis in South Africa (655 children), Malawi (701 children), and Kenya (1599 children). Patients were assigned to groups according to whether the diagnosis was culture-confirmed tuberculosis, culture-negative tuberculosis, diseases other than tuberculosis, or latent tuberculosis infection. Diagnostic signatures distinguishing tuberculosis from other diseases and from latent tuberculosis infection were identified from genomewide analysis of RNA expression in host blood.

RESULTS: We identified a 51-transcript signature distinguishing tuberculosis from other diseases in the South African and Malawian children (the discovery cohort). In the Kenyan children (the validation cohort), a risk score based on the signature for tuberculosis and for diseases other than tuberculosis showed a sensitivity of 82.9% (95% confidence interval [CI], 68.6 to 94.3) and a specificity of 83.6% (95% CI, 74.6 to 92.7) for the diagnosis of culture-confirmed tuberculosis. Among patients with cultures negative for Mycobacterium tuberculosis who were treated for tuberculosis (those with highly probable, probable, or possible cases of tuberculosis), the estimated sensitivity was 62.5 to 82.3%, 42.1 to 80.8%, and 35.3 to 79.6%, respectively, for different estimates of actual tuberculosis in the groups. In comparison, the sensitivity of the Xpert MTB/RIF assay for molecular detection of M. tuberculosis DNA in cases of culture-confirmed tuberculosis was 54.3% (95% CI, 37.1 to 68.6), and the sensitivity in highly probable, probable, or possible cases was an estimated 25.0 to 35.7%, 5.3 to 13.3%, and 0%, respectively; the specificity of the assay was 100%.

CONCLUSIONS: RNA expression signatures provided data that helped distinguish tuberculosis from other diseases in African children with and those without HIV infection.
Keyword Medicine, General & Internal
General & Internal Medicine
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
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Created: Tue, 27 May 2014, 12:38:57 EST by System User on behalf of Institute for Molecular Bioscience