TABLE 1

Summary of the World Health Organization (WHO) standards for early detection, diagnosis and treatment of tuberculosis (TB) (susceptible and drug-resistant) and latent tuberculosis infection (LTBI)

Standards for early TB detection
 1) For persons with signs or symptoms consistent with TB, performing prompt clinical evaluation is essential to ensure early and rapid diagnosis [10, 11].
 2) All persons who have been in close contact with patients who have pulmonary TB should be evaluated. The highest priority contacts for evaluation are those [3]:
    with signs or symptoms suggestive of TB;
    aged <5 years;
    with known or suspected immunocompromising conditions, particularly HIV infection;
    who have been in contact with patients with MDR-TB or XDR-TB.
 3) All persons living with HIV and workers who are exposed to silica should always be screened for active TB in all settings. Other high-risk groups should be prioritised for screening based on the local TB epidemiology, health system capacity, resource availability and feasibility of reaching the risk groups [3, 12].
 4) CXR is an important tool for triaging and screening for pulmonary TB, and it is also useful to aid diagnosis when pulmonary TB cannot be confirmed bacteriologically. CXR can be used to select individuals for referral for bacteriological confirmation and the role of radiology remains important when bacteriological tests cannot provide a clear answer [3, 13, 14].
Standards for TB diagnosis
 5) To safely and efficiently diagnose TB and drug-resistant TB requires a functional network of quality-assured laboratories with appropriate biosafety measures in place for performing different technical procedures. As such, TB programmes require a tiered network of integrated laboratories in which different levels use complementary tools to diagnose TB and HIV, and have mechanisms for referring specimens between the different levels of the network [3, 15].
 6) All patients with signs and symptoms of pulmonary TB who are capable of producing sputum should have as their initial diagnostic test at least one sputum specimen submitted for Xpert MTB/RIF Ultra assay. This includes children who are able to provide a sputum sample and patients with EPTB. A second Xpert MTB/RIF Ultra assay may be performed for all patients who initially test negative by Xpert MTB/RIF Ultra but whose signs and symptoms of TB persist [3, 16].
 7) The Xpert MTB/RIF Ultra assay should be used in preference to conventional microscopy and culture as the initial diagnostic test for cerebrospinal fluid specimens from patients being evaluated for TB meningitis. The Xpert MTB/RIF Ultra assay is recommended as a replacement test for usual practice (including conventional microscopy, culture or histopathology) for testing specific nonrespiratory specimens (lymph nodes and other tissues) from patients suspected of having EPTB [3].
 8) For persons living with HIV, the Xpert MTB/RIF Ultra assay should be used as an initial diagnostic test. LF-LAM can be used to assist in the diagnostic process for HIV-positive patients who are seriously ill [3, 17–19].
 9) DST using WHO-recommended rapid tests should be performed for all TB patients prior to starting therapy, including new patients and patients who require retreatment. If rifampicin resistance is detected, rapid molecular tests for resistance to isoniazid, fluoroquinolones and second-line injectable agents should be performed promptly to inform the treatment of MDR-TB and XDR-TB [3, 20–22].
 10) Culture-based DST for selected second-line anti-TB agents should be performed for patients enrolled in individualised (longer) MDR-TB treatment [3].
Standard for diagnosing LTBI
 11) Either TST or IGRA can be used to test for LTBI. TST is not required before initiating IPT in persons living with HIV [23].
Standards for treating drug-susceptible TB
 12) While awaiting DST results, patients with drug-susceptible TB and TB patients who have not been treated previously with anti-TB agents and do not have other risk factors for drug resistance should receive a WHO-recommended first-line treatment regimen using quality assured anti-TB agents. The initial phase should consist of 2 months of isoniazid, rifampicin, pyrazinamide and ethambutol. The continuation phase should consist of 4 months of isoniazid and rifampicin. Daily dosing should be used throughout treatment. The doses of anti-TB agents should conform to WHO's recommendations. FDC anti-TB agents may provide a more convenient form of administration [3, 24–26].
 13) In patients who require retreatment for TB, the category II regimen should no longer be prescribed and DST should be conducted to inform the choice of treatment regimen [3].
 14) In patients with tuberculous meningitis or tuberculous pericarditis, adjuvant corticosteroid therapy should be used in addition to an appropriate TB treatment regimen [3].
Standards for treating drug-resistant TB
 15) In patients with rifampicin-susceptible, isoniazid-resistant TB, 6 months of combination treatment with rifampicin, ethambutol, pyrazinamide and levofloxacin, with or without isoniazid, is recommended [3, 25, 26].
 16) Patients with MDR/RR-TB require second-line treatment regimens. MDR/RR-TB patients may be treated using a 9–11-month MDR-TB treatment regimen (the shorter regimen) unless they have resistance to second-line anti-TB agents or meet other exclusion criteria. In these cases, a longer (individualised) regimen with at least five effective anti-TB agents in the intensive phase and four agents in the continuation phase is recommended for ≥20 months. Partial resection surgery has a role in treating MDR-TB [3, 25].
 17) A system to actively monitor and manage harms caused by anti-TB agents is required whenever drug-resistant TB patients are treated with novel or repurposed medicines and MDR-TB regimens [3, 27].
Standard for treating LTBI
 18) Persons living with HIV and children younger than 5 years who are household or close contacts of persons with TB and who, after an appropriate clinical evaluation, are found not to have active TB but to have LTBI should be treated [3, 23].

MDR: multidrug-resistant; XDR: extensively drug-resistant; CXR: chest radiography; EPTB: extrapulmonary tuberculosis; LF-LAM: lateral-flow urine lipoarabinomannan assay; DST: drug susceptibility testing; TST: tuberculin skin test; IGRA: interferon-γ release assay; IPT: isoniazid preventative therapy; FDC: fixed-dose combination; RR: rifampicin-resistant.