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Table 2 Diagnostic tests for pulmonary tuberculosis: current, under evaluation and in development

From: The role of rapid diagnostic tests in managing adults with pneumonia in low-resource settings

Test

Comments

Ref

Chest radiography

Used as adjunct to smear microscopy. No radiographic pattern diagnostic of TB and substantial inter-observer variation. Appearances vary with immune status in HIV-associated disease.

23

Sputum smear microscopy

Rapid and widely available; often sole diagnostic test. Sensitivity is poor, particularly in HIV-associated TB; increased by sputum concentration and fluorescence microscopy rather than ZN staining.

23

Sputum culture

Gold-standard diagnostic test; often restricted to reference centres in resource-limited settings. Automated liquid culture systems (e.g. BACTEC MGIT 960; Becton Dickinson, USA) are faster and more sensitive than solid culture techniques.

23

Xpert MTB/RIF (Cepheid, USA)

Fully automated NAAT platform; allows rapid detection of MDRTB. More sensitive than sputum smear microscopy, particularly in HIV-infection. High setup and running costs; needs uninterrupted electrical supply.

22

Line probe assay (e.g. GenoType MTBDRplus 2.0; Hain Lifescience GmbH, Germany)

NAAT mainly used for rapid identification of isoniazid mono-resistance and MDRTB in culture isolates. Now adapted for use on clinical specimens; comparable accuracy to Xpert MTB/RIF.

24

Loop-mediated isothermal amplification

Simplified, manual NAAT for use in basic laboratory settings. Currently in large scale evaluation; estimated sensitivity is 88% overall and 56% in sputum smear-negative TB.

25

Urinary lipoarabinomannan (e.g. Alere Determine TB LAM Ag; Alere, USA)

POC assay facilitating rapid treatment initiation. Most sensitive in advanced HIV-infection; incremental increase in sensitivity over sputum smear microscopy and Xpert MTB/RIF alone.

26, 27

Volatile organic compounds

Mass spectrographic analysis of exhaled breath for compounds associated with pulmonary TB. In early stages of development; requires sophisticated instrumentaion.

21

Serological tests

Humoral response to TB is highly variable; no single antibody measurement proved useful in diagnosis. Assays based on simultaneous detection of multiple antibodies in development.

21

Proteomics

Serum proteomic profile of active TB derived by mass spectrometry. Diagnostic tests based on candidate biomarkers in development.

21

  1. TB, tuberculosis; ZN, Ziehl-Neelsen; NAAT, nucleic-acid amplification test; MDRTB, multi-drug resistant tuberculosis; POC, point-of-care.