Blood transcriptomic signatures for symptomatic tuberculosis in an African multicohort study.

Area of Science:

• Genomics
• Infectious Diseases
• Diagnostics

Background:

• Tuberculosis (TB) diagnosis often relies on sputum, necessitating alternative non-sputum methods.
• Host blood transcriptional signatures are being explored as potential triage tests for TB.

Purpose of the Study:

• To compare the diagnostic performance of 20 blood transcriptomic signatures.
• To differentiate between tuberculosis (TB) and other respiratory diseases (ORD) in symptomatic patients.

Main Methods:

• A nested case-control study enrolled symptomatic individuals from primary healthcare clinics across six African countries.
• TB diagnosis was confirmed through clinical, microbiological, and radiological assessments.
• Whole blood transcriptomic signatures were measured using microfluidic real-time quantitative PCR.

Main Results:

• Nine signatures showed comparable performance in differentiating TB from ORD (AUCs ranging from 0.79 to 0.83).
• Specificities ranged from 44% to 54% at 90% sensitivity, not meeting the World Health Organization Target Product Profile (TPP) criteria.
• Signature performance varied significantly by HIV status and country; some signatures met TPP criteria in specific countries like Ethiopia, Malawi, and South Africa.

Conclusions:

• No single blood transcriptomic signature met the TPP criteria for a non-sputum TB triage test across all evaluated countries in a pooled analysis.
• However, certain signatures demonstrated potential as triage tests in country-specific contexts, warranting further investigation.