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Updated: Apr 30, 2026
A Tuberculosis Molecular Bacterial Load Assay TB-MBLA
Published on: April 30, 2020
Diagnosis of childhood tuberculosis and host RNA expression in Africa
Insights
Researchers identified a novel 51-transcript RNA signature in blood to diagnose tuberculosis in African children. This host-based biomarker shows promise for distinguishing tuberculosis from other diseases, aiding in diagnosis for children with and without HIV.
Area of Science:
- Molecular diagnostics
- Infectious disease epidemiology
- Pediatric infectious diseases
Background:
- Tuberculosis (TB) diagnosis in children, particularly in Africa, requires improved methods.
- Host transcriptional signatures in blood are explored as a potential diagnostic tool.
- The study considers children with and without human immunodeficiency virus (HIV) infection.
Purpose of the Study:
- To develop and validate a host-based diagnostic signature for tuberculosis in African children.
- To differentiate tuberculosis from other diseases and latent tuberculosis infection using RNA expression.
- To assess the signature's performance in diverse African pediatric populations.
Main Methods:
- Prospective cohort studies in South Africa, Malawi, and Kenya involving children evaluated for suspected tuberculosis.
- Genome-wide RNA expression analysis of host blood to identify diagnostic signatures.
- Validation of a risk score based on the identified signature in a separate cohort.
Main Results:
- A 51-transcript signature was identified that distinguishes tuberculosis from other diseases.
- In the validation cohort, the signature-based risk score achieved 82.9% sensitivity and 83.6% specificity for culture-confirmed tuberculosis.
- The signature demonstrated improved sensitivity compared to Xpert MTB/RIF assay in certain pediatric TB case definitions.
Conclusions:
- Host RNA expression signatures can effectively distinguish tuberculosis from other diseases in African children.
- The findings support the potential utility of transcriptional signatures as a non-invasive diagnostic biomarker for pediatric tuberculosis.
- This approach holds promise for improving TB diagnosis in resource-limited settings, including for HIV-infected children.
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).
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