5.1 Guidance for using of diagnostic algorithm

Adolescents are defined in this chapter as patients aged 10 years or more.

Signs and symptoms of pulmonary tuberculosis (PTB)

• If HIV infection, any of the following: current cough, fever, weight loss or night sweats.
• If no HIV infection, any of the following: cough for more than 2 weeks, cough with haemoptysis, unexplained weight loss, night sweats or clinical suspicion.

LF-LAM

• The lateral flow urine lipoarabinomannan assay (LF-LAM) should be performed only in patients with HIV infection.
• Irrespective of the LF-LAM result, a rapid molecular test (RMT) should also be performed because:
  • An RMT could be positive (better sensitivity) if the LF-LAM is negative.
  • An RMT can also detect rifampicin resistance.

Xpert MTB/RIF 

• A second Xpert MTB/RIF (or Ultra) should be performed on a new specimen if the first test shows:
  • "Error/Invalid/No result"
  • "MTB detected; Rif resistance indeterminate" a Citation a. If the second test is still "Rif indeterminate", perform a pDST or another gDST to confirm or rule out rifampicin resistance.
  • "MTB not detected" (according to clinical judgement, e.g. high index of clinical suspicion, no response to short course of antibiotic treatment for pneumonia)
  • "MTB detected; Rif resistance detected" in patient with low risk of rifampicin resistance (i.e. no previous TB treatment with rifampicin, no contact with a TB case resistant to rifampicin, and coming from an area of low prevalence of resistance to rifampicin)
• If an Xpert MTB/RIF Ultra is used and the result is "trace", a second test should be performed on a new specimen, except in the following circumstances:
  • Patients with HIV infection, children and EP specimens: the result is considered positive. The test should not be repeated.
  • Adults with history of TB in the previous 5 years: a "trace" result cannot be interpreted. Culture should be performed. 
• No interpretation of RR is possible. If resistance to rifampicin or other TB drugs is suspected: phenotypic drug-susceptibility test (pDST) or another genotypic DST (gDST) should be performed.
• Xpert MTB/RIF and Xpert MTB/RIF Ultra assays can be replaced by Truenat assays.
• If RMTs are not immediately available, send a specimen for RMT to the local reference laboratory. Perform sputum microscopy and chest x-ray (CXR) if available. While waiting for RMT result, if sputum microscopy is positive, or CXR suggestive of TB, start TB treatment according to previous treatment, contact history and local epidemiology.

Xpert MTB/XDR 

• A second Xpert MTB/XDR should be performed on a new specimen if the first test shows:
  • "Error/Invalid/No result"
  • "MTB detected; drug resistance indeterminate"
  • "MTB not detected" after a positive Xpert MTB/RIF
  • "MTB detected; drug resistance detected" in patient with low risk of drug resistance (i.e. no previous TB treatment with the drug, no contact with a TB case resistant to the drug, and coming from an area of low prevalence of resistance to the drug)
• The Xpert MTB/XDR should not be performed if the result of Xpert MTB/RIF Ultra was "trace" on two specimens. A pDST or another gDST should be performed.
• If Xpert MTB/XDR is not immediately available, and the reference laboratory does not perform this test, request a line probe assay (LPA) or a pDST.

CXR

Abnormalities suggestive of PTB include:

• Infiltrates located in upper lobes and superior segments of lower lobes
• Cavities
• Consolidations (patchy or confluent)
• Mediastinal and hilar lymphadenopathy
• Miliary pattern.

See also Medical imaging, Chapter 3.

pDST (and NGS)

A pDST and, if available, a next generation sequencing (NGS) should be performed in all patients with MDR/RR-TB to detect potential resistance to bedaquiline, linezolid and other drugs not tested by RMTs.