Host RNA Expression Diagnoses Childhood Tuberculosis

Tuberculosis (TB) is notoriously difficult to diagnose in children and when it is diagnosed, the disease is often in its late stages and has already spread to the brain and other organs, increasing the risk of death.

The use of genomewide ribonucleic acid (RNA) expression in host blood to distinguish tuberculosis from other diseases that are prevalent among African children with and those without human immunodeficiency virus (HIV) infection has been explored.

An international team of scientists led by those at Imperial College London (UK) analyzed more than 2,800 children from Malawi, Kenya, and South Africa. All children had been admitted to the hospital with symptoms of TB. They then established which children had proven TB and which children had been cleared of the disease. Patients were recruited between February 17, 2008, and January 27, 2011.

Two spontaneous or induced sputum samples and a specimen of tissue or cerebrospinal fluid (if clinically indicated) were examined for acid-fast bacilli and cultured for mycobacteria. The Xpert MTB/RIF21 (Cepheid; Sunnyvale, CA, USA) real-time polymerase chain reaction (PCR) assay, which is a test for Mycobacterium tuberculosis and resistance to rifampin, was performed on respiratory samples in the Kenyan cohort. Whole blood was collected extracted with the use of PAXgene Blood RNA Kits (Qiagen; Venlo, the Netherlands) and analyzed on HumanHT-12 v.4 Expression BeadChip arrays (Illumina; San Diego, CA, USA).

The team identified a tuberculosis-specific transcriptome signature in host blood that appears to be valuable in distinguishing tuberculosis from other diseases with similar clinical features in HIV-positive and HIV-negative African children. The risk score identified higher proportions of culture-confirmed cases of tuberculosis and culture-negative cases than did the Xpert MTB/RIF assay. The risk score was also more sensitive than the interferon-γ–release assay (IGRA) and the C-reactive protein level proved to be a poor biomarker of childhood tuberculosis. By looking at 51 specific genes in the blood of children with TB, the disease can be identified in 80% of cases.

The authors concluded that the translation of transcriptional signatures into diagnostic tools in resource-poor communities will be challenging and innovation will be needed to reduce the cost and complexity of the current methods used to detect multiple RNA transcripts. The development of a test based on this risk score for tuberculosis could improve the diagnosis and surveillance of childhood tuberculosis in areas with a high or low burden of disease. The study was published on May 1, 2014, in the New England Journal of Medicine.

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Imperial College London
Cepheid
Qiagen