Active tuberculosis — MSF Tuberculosis

What this guideline says

GMJ summary

This MSF guideline section provides detailed recommendations for the diagnosis of active tuberculosis through bacteriological confirmation, drug susceptibility testing and supportive investigations. The guideline prioritizes rapid molecular tests (RMTs) as the initial diagnostic approach for all patients with presumed TB, replacing microscopy as the first-line test. All patients with confirmed TB should undergo drug susceptibility testing, with priority given to patients at high risk of mortality (HIV infection, extensive disease) or high risk of resistance (previous TB treatment, contact with drug-resistant cases, or from high-prevalence areas).

The guideline comprehensively describes the performance characteristics and appropriate use of multiple diagnostic platforms, including Xpert MTB/RIF and Ultra, Xpert MTB/XDR, Truenat assays, line probe assays, genome sequencing, culture and phenotypic drug susceptibility testing. Xpert MTB/RIF Ultra is preferred for patients with HIV infection, children, extrapulmonary specimens and smear-negative specimens due to higher sensitivity, though specificity is lower in patients with previous TB history. The lateral flow urine lipoarabinomannan assay (LF-LAM) is recommended for specific HIV-positive patient groups as a rapid point-of-care test.

The guideline emphasizes that negative bacteriological tests do not rule out TB, and that drug susceptibility testing may require multiple modalities (genotypic and phenotypic) depending on the drug and local resistance patterns. Chest X-ray remains important for detecting abnormalities suggestive of pulmonary TB, evaluating severity and monitoring treatment response, with digital radiography and computer-aided detection increasingly useful in programmatic settings.

Key points

For clinicians — doses and thresholds as stated in the guideline

1. All patients with presumed TB should be tested with a rapid molecular test (RMT) to detect M. tuberculosis and rifampicin resistance; when microscopy is the only diagnostic test available, specimens should be sent to a facility with capacity to perform RMTs
2. Xpert MTB/RIF Ultra has higher sensitivity than Xpert MTB/RIF (+ 5%) but lower specificity (- 3.2% overall, – 5.4% in patients with TB history); it provides a 'trace' result for lowest bacillary load but may indicate dead bacilli in those with previous TB
3. Drug susceptibility testing is indicated for all patients with confirmed TB; priority should be given to patients with high risk of mortality (HIV infection, extensive disease) or high risk of resistance (previous TB treatment, contact with resistant case, or from high-prevalence area)
4. LF-LAM testing is recommended for: HIV-infected patients with signs/symptoms of TB or seriously ill (respiratory rate > 30/min, temperature > 39 °C, heart rate > 120/min, unable to walk unaided); inpatients with advanced HIV disease (CD4 < 200 cells/mm³ or WHO stage 3/4); and outpatients with HIV and CD4 < 100 cells/mm³
5. Xpert MTB/XDR should be used to detect isoniazid resistance in all patients if possible, and at least those with high risk; to detect fluoroquinolone resistance before using fluoroquinolone-containing regimens; and to detect resistance to isoniazid, fluoroquinolones, aminoglycosides and thionamides when rifampicin resistance is detected
6. Smear microscopy has 65% sensitivity compared to culture and approximately 86% of smear-positive patients are identified during the first examination, with an additional 12% during the second; more than two examinations are not necessary
7. Phenotypic DST is highly reliable for isoniazid, rifampicin, fluoroquinolones and aminoglycosides; unreliable for ethambutol, ethionamide, cycloserine/terizidone and para-aminosalicylic acid; reliable but with limited access for bedaquiline, linezolid, clofazimine and delamanid
8. For pleural effusion, adenosine deaminase (ADA) > 50 U/litre with lymphocyte-neutrophil ratio > 0.75 increases specificity for TB; for peritoneal fluid, ADA > 39 U/litre is likely due to TB; pleural effusion with ADA < 40 U/litre is much less likely TB

Table 3.2 – Main performances of Xpert assays

Table extracted from the guideline

Source: Médecins Sans Frontières, Active tuberculosis — MSF Tuberculosis. Reproduced in summary form.

From the guideline

Verbatim

“Drug susceptibility testing (DST) is indicated for all patients with confirmed TB.”

Editor’s perspective

Why this matters for Georgia and the region

Applicability

Georgia and the South Caucasus

Questions this guideline answers

Quick answers

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