Guideline

WHO consolidated guidelines on tuberculosis: module 3: diagnosis

Year of Publication

2025

Issuing Institution

World Health Organization

Links

WHO IRIS

Recommendations

25 included recommendations

For adults and adolescents with signs or symptoms of TB or who screened positive for pulmonary TB, low-complexity automated nucleic acid amplification tests should be used on respiratory samples as initial diagnostic tests for TB, rather than smear microscopy or culture

Status

Updated

Recommended in favor

Strong

Certainty of evidence

High

For people with bacteriologically confirmed TB, low-complexity automated nucleic acid amplification tests should be used on respiratory samples as initial tests for detection of resistance to rifampicin, rather than culture-based drug susceptibility testing.

Status

Updated

Recommended in favor

Strong

Certainty of evidence

High

For people with signs and symptoms of TB meningitis, low-complexity automated nucleic acid amplification tests on cerebral spinal fluid should be used for the initial diagnosis of TB meningitis, rather than smear microscopy or culture.

Status

Updated

Recommended in favor

Strong

Certainty of evidence

Moderate

For people with signs and symptoms of extrapulmonary TB, low-complexity automated nucleic acid amplification tests on lymph node tissue aspirate, pleural tissue, pleural fluid, synovial fluid, peritoneal fluid or pericardial fluid should be used for the initial diagnosis of TB, rather than smear microscopy or culture.

Status

Updated

Recommended in favor

Strong

For people with signs and symptoms of pulmonary TB, moderate-complexity automated nucleic acid amplification tests may be used on respiratory samples for the detection of pulmonary TB, and of rifampicin and isoniazid resistance, rather than culture and phenotypic drug susceptibility testing.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Moderate

For adults and adolescents with signs or symptoms or who screen positive for pulmonary TB, low-complexity manual nucleic acid amplification tests should be used on respiratory samples as initial diagnostic tests for TB, rather than smear microscopy or culture.

Status

Updated

Recommended in favor

Strong

Certainty of evidence

High

For adults and adolescents with HIV who have signs or symptoms of TB, screen positive for TB, are seriously ill or have advanced HIV disease, concurrent testing using low-complexity automated nucleic acid amplification tests (NAATs) on respiratory samples and LF-LAM on urine should be used as the initial diagnostic strategy for diagnosing TB, rather than low complexity automated NAATs on respiratory samples alone.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Low

For children who are HIV-negative or have an unknown HIV status, who have signs or symptoms or screen positive for pulmonary TB, concurrent testing using low complexity automated nucleic acid amplification tests (NAATs) on respiratory and stool samples should be used as the initial diagnostic strategy for diagnosing TB, rather than low-complexity automated NAATs on respiratory or stool samples alone.

Status

Updated

Recommended in favor

Strong

Certainty of evidence

Low

For children with HIV who have signs or symptoms or screen positive for pulmonary TB, concurrent testing using low-complexity automated nucleic acid amplification tests (NAATs) on respiratory and stool samples and LF-LAM on urine may be used as the initial diagnostic strategy for diagnosing TB, rather than low-complexity automated NAATs on respiratory or stool samples alone

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

In people with bacteriologically confirmed pulmonary TB, low complexity automated NAATs may be used on sputum for the initial detection of resistance to isoniazid and fluoroquinolones, rather than culture-based phenotypic DST

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Moderate

In people with bacteriologically confirmed pulmonary TB and resistance to rifampicin, low complexity automated NAATs may be used on sputum for the initial detection of resistance to ethionamide, rather than DNA sequencing of the inhA promoter

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

In people with bacteriologically confirmed pulmonary TB and resistance to rifampicin, low complexity automated NAATs may be used on sputum for the initial detection of resistance to amikacin, rather than culture-based phenotypic DST

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

For persons with a sputum smear-positive specimen or a cultured isolate of MTBC, commercial molecular LPAs may be used as the initial test instead of phenotypic culture-based DST to detect resistance to rifampicin and isoniazid.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Moderate

For patients with confirmed rifampicin-resistant TB (tuberculosis) or MDR-TB (multidrug resistant tuberculosis), SL-LPA (Second-line lineprobe assays) may be used as the initial test, instead of phenotypic culture-based DST (drug-susceptibility testing), to detect resistance to fluoroquinolones

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

For patients with confirmed rifampicin-resistant TB (tuberculosis) or MDR-TB (multidrug resistant tuberculosis), SL-LPA (Second-line lineprobe assays) may be used as the initial test, instead of phenotypic culture-based DST DST (drug-susceptibility testing), to detect resistance to the second-line injectable drugs

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

In people with bacteriologically confirmed TB, high complexity reverse hybridization based NAATs may be used on Mtb culture isolates for detection of pyrazinamide resistance rather than culture-based phenotypic DST.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

In people with bacteriologically confirmed pulmonary TB disease, targeted next generation sequencing technologies may be used on respiratory samples to diagnose resistance to isoniazid and pyrazinamide rather than culture-based phenotypic drug susceptibility testing

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Moderate

In people with bacteriologically confirmed pulmonary TB disease, targeted next generation sequencing technologies may be used on respiratory samples to diagnose resistance to rifampicin, fluoroquinolones, and ethambutol rather than culture-based phenotypic drug susceptibility testing

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

In people with bacteriologically confirmed rifampicin-resistant pulmonary TB disease, targeted next generation sequencing technologies may be used on respiratory samples to diagnose resistance to isoniazid, fluoroquinolones and pyrazinamide rather than culture-based phenotypic drug susceptibility testing.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

High

In people with bacteriologically confirmed rifampicin-resistant pulmonary TB disease, targeted next generation sequencing technologies may be used on respiratory samples to diagnose resistance to ethambutol rather than culture-based phenotypic drug susceptibility testing.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Moderate

In people with bacteriologically confirmed rifampicin-resistant pulmonary TB disease, targeted next generation sequencing technologies may be used on respiratory samples to diagnose resistance to bedaquiline, linezolid, clofazimine and streptomycin rather than culture-based phenotypic drug susceptibility testing.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

In people with bacteriologically confirmed rifampicin-resistant pulmonary TB disease, targeted next generation sequencing technologies may be used on respiratory samples to diagnose resistance to amikacin rather than culture-based phenotypic drug susceptibility testing.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

Mycobacterium tuberculosis antigen-based skin tests (TBSTs) may be used to test for TB infection.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

Either a tuberculin skin test (TST) or interferon-gamma release assay (IGRA) can be used to test for latent tuberculosis infection (LTBI)

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Very low

interferon-gamma release assays tuberculosis interferon-gamma release assays (IGRAs) (and the TST) should not be used in low- and middle-income countries for the diagnosis of pulmonary or extra-pulmonary TB, nor for the diagnostic work-up of adults (including HIV-positive individuals) suspected of active TB in these settings (strong recommendation). This recommendation places a high value on avoiding the consequences of unnecessary treatment (high false-positives) given the low specificity of tuberculosis interferon-gamma release assays (IGRAs) (and the TST) in these settings.

Status

Maintained

Recommended against

Strong

Certainty of evidence

Very low