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, Levin, Michael and Eley, Brian (2014) 'Diagnosis of Childhood Tuberculosis and Host RNA Expression in Africa'. New England Journal of Medicine, Vol 370, Issue 18, pp. 1712-1723.

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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. (Funded by the European Union Action for Diseases of Poverty Program and others).

Item Type:	Article
Additional Information:	“From N Engl J Med, Anderson, S.T. et al, Diagnosis of Childhood Tuberculosis and Host RNA Expression in Africa, Volume No.370, Page No. 1712-1723 Copyright © (2014) Massachusetts Medical Society. Reprinted with permission.
Subjects:	QU Biochemistry > Proteins. Amino Acids. Peptides > QU 58.7 RNA WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General) WF Respiratory System > Tuberculosis > WF 220 Diagnosis. Prognosis WS Pediatrics > Diseases of Children and Adolescents > By System > WS 280 Respiratory system
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1056/NEJMoa1303657
Depositing User:	Lynn Roberts-Maloney
Date Deposited:	26 May 2015 10:56
Last Modified:	06 Feb 2018 13:09
URI:	https://archive.lstmed.ac.uk/id/eprint/5157

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