Remember Me
Or use your Academic/Social account:


Or use your Academic/Social account:


You have just completed your registration at OpenAire.

Before you can login to the site, you will need to activate your account. An e-mail will be sent to you with the proper instructions.


Please note that this site is currently undergoing Beta testing.
Any new content you create is not guaranteed to be present to the final version of the site upon release.

Thank you for your patience,
OpenAire Dev Team.

Close This Message


Verify Password:
Verify E-mail:
*All Fields Are Required.
Please Verify You Are Human:
fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
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 (2014)
Publisher: Massachusetts Medical Society
Languages: English
Types: Article
Subjects: R, ws_280, wf_200, wa_395, wf_220, qu_58.7, Article
Background\ud \ud 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).\ud \ud Methods\ud \ud 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.\ud \ud Results\ud \ud 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%.\ud \ud Conclusions\ud \ud 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).
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • 1. Perez-Velez CM, Marais BJ. Tuberculosis in children. N Engl J Med 2012;367:348-61.
    • 2. Global tuberculosis report 2012. Geneva: World Health Organization, 2012.
    • 3. Zar HJ, Connell TG, Nicol M. Diagnosis of pulmonary tuberculosis in children: new advances. Expert Rev Anti Infect Ther 2010;8:277-88.
    • 4. Marais BJ, Gie RP, Obihara CC, Hesseling AC, Schaaf HS, Beyers N. Well defined symptoms are of value in the diagnosis of childhood pulmonary tuberculosis. Arch Dis Child 2005;90:1162-5.
    • 5. Hatherill M, Hanslo M, Hawkridge T, et al. Structured approaches for the screening and diagnosis of childhood tuberculosis in a high prevalence region of South Africa. Bull World Health Organ 2010;88: 312-20.
    • 6. Hesseling AC, Schaaf HS, Gie RP, Starke JR, Beyers N. A critical review of diagnostic approaches used in the diagnosis of childhood tuberculosis. Int J Tuberc Lung Dis 2002;6:1038-45.
    • 7. Pearce EC, Woodward JF, Nyandiko WM, Vreeman RC, Ayaya SO. A systematic review of clinical diagnostic systems used in the diagnosis of tuberculosis in children. AIDS Res Treat 2012;2012:401896.
    • 8. Cuevas LE, Petrucci R, Swaminathan S. Tuberculosis diagnostics for children in high-burden countries: what is available and what is needed. Paediatr Int Child Health 2012;32:Suppl 2:S30-S37.
    • 9. Drobac PC, Shin SS, Huamani P, et al. Risk factors for in-hospital mortality among children with tuberculosis: the 25-year experience in Peru. Pediatrics 2012;130(2): e373-e379.
    • 10. Chintu C, Mudenda V, Lucas S, et al. Lung diseases at necropsy in African children dying from respiratory illnesses: a descriptive necropsy study. Lancet 2002; 360:985-90.
    • 11. Zar HJ, Hanslo D, Apolles P, Swingler G, Hussey G. Induced sputum versus gastric lavage for microbiological confirmation of pulmonary tuberculosis in infants and young children: a prospective study. Lancet 2005;365:130-4. [Erratum, Lancet 2005;365:1926.]
    • 12. Swingler GH, du Toit G, Andronikou S, van der Merwe L, Zar HJ. Diagnostic accuracy of chest radiography in detecting mediastinal lymphadenopathy in suspected pulmonary tuberculosis. Arch Dis Child 2005;90:1153-6.
    • 13. Machingaidze S, Wiysonge CS, Gonzalez-Angulo Y, et al. The utility of an interferon gamma release assay for diagnosis of latent tuberculosis infection and disease in children: a systematic review and meta-analysis. Pediatr Infect Dis J 2011; 30:694-700.
    • 14. Mandalakas AM, Detjen AK, Hesseling AC, Benedetti A, Menzies D. Interferongamma release assays and childhood tuberculosis: systematic review and metaanalysis. Int J Tuberc Lung Dis 2011;15: 1018-32.
    • 15. Eamranond P, Jaramillo E. Tuberculosis in children: reassessing the need for improved diagnosis in global control strategies. Int J Tuberc Lung Dis 2001;5: 594-603.
    • 16. Graham SM, Marais BJ, Gie RP. Clinical features and index of suspicion of tuberculosis in children. In: Schaaf HS, Zumla A, eds. Tuberculosis: a comprehensive reference. Philadelphia: Saunders Elsevier, 2009:154-63.
    • 17. Kampmann B, Whittaker E, Williams A, et al. Interferon-gamma release assays do not identify more children with active tuberculosis than the tuberculin skin test. Eur Respir J 2009;33:1374-82.
    • 18. Brent AJ. Childhood TB surveillance: bridging the knowledge gap to inform policy. J Trop Med 2012;2012:865436.
  • No related research data.
  • No similar publications.

Share - Bookmark

Funded by projects

  • WT | Quadruple intervention again...
  • WT | Malawi-Liverpool-Wellcome Tr...
  • WT | Establishment of a Centre fo...

Cite this article