Guideline

WHO consolidated guidelines on tuberculosis: module 3: diagnosis – rapid diagnostics for tuberculosis detection: web annex 2. GRADE profiles

Year of Publication

2020

Issuing Institution

WHO

Links

WHO IRIS

Recommendations

82 included recommendations

In adults with signs and symptoms of pulmonary TB, Xpert MTB/RIF should be used as an initial diagnostic test for TB and rifampicin-resistance detection in sputum rather than smear microscopy/culture and phenotypic DST.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

High

In children with signs and symptoms of pulmonary TB, Xpert MTB/RIF should be used as an initial diagnostic test for TB and rifampicin-resistance detection in sputum, gastric aspirate, nasopharyngeal aspirate and stool rather than smear microscopy/culture and phenotypic DST.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Low

In adults with signs and symptoms of pulmonary TB and without a prior history of TB (≤5 years) or with a remote history of TB treatment (>5 years since end of treatment), Xpert Ultra should be used as an initial diagnostic test for TB and for rifampicin-resistance detection in sputum, rather than smear microscopy/culture and phenotypic DST.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

High

In adults with signs and symptoms of pulmonary TB and with a prior history of TB and an end of treatment within the last 5 years, Xpert Ultra may be used as an initial diagnostic test for TB and for rifampicin-resistance detection in sputum, rather than smear microscopy/culture and phenotypic DST.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

In children with signs and symptoms of pulmonary TB, Xpert Ultra should be used as the initial diagnostic test for TB and detection of rifampicin resistance in sputum or nasopharyngeal aspirate, rather than smear microscopy/culture and phenotypic DST

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Very low

In adults and children with signs and symptoms of TB meningitis, Xpert MTB/RIF or Xpert Ultra should be used in cerebrospinal fluid (CSF) as an initial diagnostic test for TB meningitis rather than smear microscopy/culture.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

In adults and children with signs and symptoms of extrapulmonary TB, Xpert MTB/RIF may be used in lymph node aspirate, lymph node biopsy, pleural fluid, peritoneal fluid, pericardial fluid, synovial fluid or urine specimens as the initial diagnostic test rather than smear microscopy/culture.

Status

Maintained

Recommended in favor

Conditional

In adults and children with signs and symptoms of extrapulmonary TB, Xpert Ultra may be used in lymph node aspirate and lymph node biopsy as the initial diagnostic test rather than smear microscopy/culture.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

In adults and children with signs and symptoms of extrapulmonary TB, Xpert MTB/RIF or Xpert Ultra should be used for rifampicin-resistance detection rather than culture and phenotypic DST.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

High

In HIV-positive adults and children with signs and symptoms of disseminated TB, Xpert MTB/RIF may be used in blood, as an initial diagnostic test for disseminated TB.

Status

Retired

Recommended in favor

Conditional

Certainty of evidence

Very low

Adults with signs and symptoms of pulmonary TB who have an Xpert Ultra trace positive result on the initial test, repeated testing with Xpert Ultra may not be used.

Status

Maintained

Recommended against

Conditional

Certainty of evidence

Very low

In children with signs and symptoms of pulmonary TB in settings with pretest probability below 5% and an Xpert MTB/RIF negative result on the initial test, repeated testing with Xpert MTB/RIF in sputum, gastric fluid, nasopharyngeal aspirate or stool specimens may not be used

Status

Maintained

Recommended against

Conditional

Certainty of evidence

Very low

In children with signs and symptoms of pulmonary TB in settings with pretest probability 5% or more and an Xpert MTB/RIF negative result on the initial test, repeated testing with Xpert MTB/RIF (for total of two tests) in sputum, gastric fluid, nasopharyngeal aspirate and stool specimens may be used.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

In children with signs and symptoms of pulmonary TB in settings with pretest probability below 5% and an Xpert Ultra negative result on the initial test, repeated testing with Xpert Ultra in sputum or nasopharyngeal aspirate specimens may not be used.

Status

Maintained

Recommended against

Conditional

Certainty of evidence

Very low

In children with signs and symptoms of pulmonary TB in settings with pretest probability 5% or more and an Xpert Ultra negative result on the first initial test, repeated one Xpert Ultra test (for a total of two tests) in sputum and nasopharyngeal aspirate specimens may be used.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

In adults in the general population who had either signs or symptoms of TB or chest radiograph with lung abnormalities or both, the Xpert MTB/RIF or Xpert Ultra may replace culture as the initial test for pulmonary TB.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

In adults in the general population who had either a positive TB symptom screen or chest radiograph with lung abnormalities or both, one Xpert Ultra test may be used rather than two Xpert Ultra tests as the initial test for pulmonary TB.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

In adults and children with signs and symptoms of pulmonary TB, the Truenat MTB or MTB Plus may be used as an initial diagnostic test for TB rather than smear microscopy/culture.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Moderate

In adults and children with signs and symptoms of pulmonary TB and a Truenat MTB or MTB Plus positive result, Truenat MTB-RIF Dx may be used as an initial test for rifampicin resistance rather than culture and phenotypic DST

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

TB-LAMP may be used as a replacement test for sputum-smear microscopy for diagnosing pulmonary TB in adults with signs and symptoms consistent with TB.

Status

Retired

Recommended in favor

Conditional

Certainty of evidence

Very low

TB-LAMP may be used as a follow-on test to smear microscopy in adults with signs and symptoms consistent with pulmonary TB, especially when further testing of sputum smear-negative specimens is necessary.

Status

Retired

Recommended in favor

Conditional

Certainty of evidence

Very 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 MDR/RR-TB, SL-LPA may be used as the initial test, instead of phenotypic culture-based DST, to detect resistance to fluoroquinolones.

Status

Maintained

Recommended in favor

Conditional

For patients with confirmed MDR/RR-TB, SL-LPA may be used as the initial test, instead of phenotypic culture-based DST, to detect resistance to the SLIDs

Status

Maintained

Recommended in favor

Conditional

In inpatient settings, WHO strongly recommends using LF-LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: with signs and symptoms of TB (pulmonary and/or extrapulmonary)

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

In inpatient settings, WHO strongly recommends using LF-LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: with advanced HIV disease or who are seriously ill

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

In inpatient settings, WHO strongly recommends using LF-LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: irrespective of signs and symptoms of TB and with a CD4 cell count of less than 200 cells/mm3

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

In outpatient settings, WHO suggests using LF-LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: with signs and symptoms of TB (pulmonary and/or extrapulmonary) or seriously ill

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

In outpatient settings, WHO suggests using LF-LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: irrespective of signs and symptoms of TB and with a CD4 cell count of less than 100 cells/mm3

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

In outpatient settings, WHO recommends against using LF-LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: without assessing TB symptoms

Status

Maintained

Recommended against

Strong

Certainty of evidence

Very low

In outpatient settings, WHO recommends against using LF-LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: without TB symptoms and unknown CD4 cell count or without TB symptoms and CD4 cell count greater than or equal to 200 cells/mm3

Status

Maintained

Recommended against

Strong

Certainty of evidence

Very low

In outpatient settings, WHO recommends against using LF-LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: without TB symptoms and with a CD4 cell count of 100–200 cells/mm3

Status

Maintained

Recommended against

Conditional

Certainty of evidence

Very low

In adults with signs and symptoms of pulmonary TB, Xpert MTB/RIF should be used as an initial diagnostic test for TB and rifampicin-resistance detection in sputum rather than smear microscopy/culture and phenotypic DST.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

High

In children with signs and symptoms of pulmonary TB, Xpert MTB/RIF should be used as an initial diagnostic test for TB and rifampicin-resistance detection in sputum, gastric aspirate, nasopharyngeal aspirate and stool rather than smear microscopy/culture and phenotypic DST.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Low

In adults with signs and symptoms of pulmonary TB and without a prior history of TB (≤5 years) or with a remote history of TB treatment (>5 years since end of treatment), Xpert Ultra should be used as an initial diagnostic test for TB and for rifampicin-resistance detection in sputum, rather than smear microscopy/culture and phenotypic DST.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

High

In adults with signs and symptoms of pulmonary TB and with a prior history of TB and an end of treatment within the last 5 years, Xpert Ultra may be used as an initial diagnostic test for TB and for rifampicin-resistance detection in sputum, rather than smear microscopy/culture and phenotypic DST.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

In children with signs and symptoms of pulmonary TB, Xpert Ultra should be used as the initial diagnostic test for TB and detection of rifampicin resistance in sputum or nasopharyngeal aspirate, rather than smear microscopy/culture and phenotypic DST

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Very low

In adults and children with signs and symptoms of TB meningitis, Xpert MTB/RIF or Xpert Ultra should be used in cerebrospinal fluid (CSF) as an initial diagnostic test for TB meningitis rather than smear microscopy/culture.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

In adults and children with signs and symptoms of extrapulmonary TB, Xpert MTB/RIF may be used in lymph node aspirate, lymph node biopsy, pleural fluid, peritoneal fluid, pericardial fluid, synovial fluid or urine specimens as the initial diagnostic test rather than smear microscopy/culture.

Status

Maintained

Recommended in favor

Conditional

In adults and children with signs and symptoms of extrapulmonary TB, Xpert Ultra may be used in lymph node aspirate and lymph node biopsy as the initial diagnostic test rather than smear microscopy/culture.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

In adults and children with signs and symptoms of extrapulmonary TB, Xpert MTB/RIF or Xpert Ultra should be used for rifampicin-resistance detection rather than culture and phenotypic DST.

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

High

In HIV-positive adults and children with signs and symptoms of disseminated TB, Xpert MTB/RIF may be used in blood, as an initial diagnostic test for disseminated TB.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

Adults with signs and symptoms of pulmonary TB who have an Xpert Ultra trace positive result on the initial test, repeated testing with Xpert Ultra may not be used.

Status

Maintained

Recommended against

Conditional

Certainty of evidence

Very low

In children with signs and symptoms of pulmonary TB in settings with pretest probability below 5% and an Xpert MTB/RIF negative result on the initial test, repeated testing with Xpert MTB/RIF in sputum, gastric fluid, nasopharyngeal aspirate or stool specimens may not be used

Status

Maintained

Recommended against

Conditional

Certainty of evidence

Very low

In children with signs and symptoms of pulmonary TB in settings with pretest probability 5% or more and an Xpert MTB/RIF negative result on the initial test, repeated testing with Xpert MTB/RIF (for total of two tests) in sputum, gastric fluid, nasopharyngeal aspirate and stool specimens may be used.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

In children with signs and symptoms of pulmonary TB in settings with pretest probability below 5% and an Xpert Ultra negative result on the initial test, repeated testing with Xpert Ultra in sputum or nasopharyngeal aspirate specimens may not be used.

Status

Maintained

Recommended against

Conditional

Certainty of evidence

Very low

In children with signs and symptoms of pulmonary TB in settings with pretest probability 5% or more and an Xpert Ultra negative result on the first initial test, repeated one Xpert Ultra test (for a total of two tests) in sputum and nasopharyngeal aspirate specimens may be used.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

In adults in the general population who had either signs or symptoms of TB or chest radiograph with lung abnormalities or both, the Xpert MTB/RIF or Xpert Ultra may replace culture as the initial test for pulmonary TB.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

In adults in the general population who had either a positive TB symptom screen or chest radiograph with lung abnormalities or both, one Xpert Ultra test may be used rather than two Xpert Ultra tests as the initial test for pulmonary TB.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

In adults and children with signs and symptoms of pulmonary TB, the Truenat MTB or MTB Plus may be used as an initial diagnostic test for TB rather than smear microscopy/culture.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Moderate

In adults and children with signs and symptoms of pulmonary TB and a Truenat MTB or MTB Plus positive result, Truenat MTB-RIF Dx may be used as an initial test for rifampicin resistance rather than culture and phenotypic DST

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

TB-LAMP may be used as a replacement test for sputum-smear microscopy for diagnosing pulmonary TB in adults with signs and symptoms consistent with TB.

Status

Retired

Recommended in favor

Conditional

Certainty of evidence

Very low

TB-LAMP may be used as a follow-on test to smear microscopy in adults with signs and symptoms consistent with pulmonary TB, especially when further testing of sputum smear-negative specimens is necessary.

Status

Retired

Recommended in favor

Conditional

Certainty of evidence

Very 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 MDR/RR-TB, SL-LPA may be used as the initial test, instead of phenotypic culture-based DST, to detect resistance to fluoroquinolones.

Status

Maintained

Recommended in favor

Conditional

For patients with confirmed MDR/RR-TB, SL-LPA may be used as the initial test, instead of phenotypic culture-based DST, to detect resistance to the SLIDs

Status

Maintained

Recommended in favor

Conditional

In inpatient settings, WHO strongly recommends using LF-LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: •with signs and symptoms of TB (pulmonary and/or extrapulmonary) (strong recommendation, moderate certainty in the evidence about the intervention effects); or •with advanced HIV disease; or •who are seriously ill (strong recommendation, moderate certainty in the evidence about the intervention effects); or •irrespective of signs and symptoms of TB and with a CD4 cell count <200 (strong recommendation, moderate certainty in the evidence about the intervention effects).

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

In inpatient settings, WHO strongly recommends using LF-LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: with advanced HIV disease or who are seriously illl

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

In inpatient settings, WHO strongly recommends using LF-LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: irrespective of signs and symptoms of TB and with a CD4 cell count of less than 200 cells/mm3

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

In outpatient settings, WHO suggests using LF-LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: with signs and symptoms of TB (pulmonary and/or extrapulmonary) or seriously ill

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

In outpatient settings, WHO suggests using LF-LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: irrespective of signs and symptoms of TB and with a CD4 cell count of less than 100 cells/mm3

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

In outpatient settings, WHO recommends against using LF-LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: without assessing TB symptoms

Status

Maintained

Recommended against

Strong

Certainty of evidence

Very low

In outpatient settings, WHO recommends against using LF-LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: without TB symptoms and unknown CD4 cell count or without TB symptoms and CD4 cell count greater than or equal to 200 cells/mm3

Status

Maintained

Recommended against

Strong

Certainty of evidence

Very low

In outpatient settings, WHO recommends against using LF-LAM to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: without TB symptoms and with a CD4 cell count of 100–200 cells/mm3

Status

Maintained

Recommended against

Conditional

Certainty of evidence

Very low

In people with signs and symptoms of pulmonary TB, moderate complexity automated NAATs may be used on respiratory samples for the detection of pulmonary TB, and of rifampicin and isoniazid resistance, rather than culture and phenotypic DST.

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Moderate

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

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

loop-mediated isothermal amplification (LAMP) may be used as a replacement test for sputum-smear microscopy to diagnose pulmonary TB in adults with signs and symptoms consistent with TB

Status

Updated

Recommended in favor

Conditional

Certainty of evidence

Very low

loop-mediated isothermal amplification (LAMP) may be used as a follow-on test to smear microscopy in adults with signs and symptoms consistent with pulmonary TB, especially when further testing of sputum smearnegative specimens is necessary

Status

Updated

Recommended in favor

Conditional

Certainty of evidence

Very low

For persons with a sputum smear-positive specimen or a cultured isolate of MTBC, commercial molecular line-probe assay (LPA) 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 inpatient settings, WHO strongly recommends using lateral flow urine lipoarabinomannan assay (LF-LAM) to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: with signs and symptoms of TB (pulmonary and/or extrapulmonary

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

In inpatient settings, WHO strongly recommends using lateral flow urine lipoarabinomannan assay (LF-LAM) to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: with advanced HIV disease or who are seriously ill

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

In inpatient settings, WHO strongly recommends using lateral flow urine lipoarabinomannan assay (LF-LAM) to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: irrespective of signs and symptoms of TB and with a CD4 cell count < 200

Status

Maintained

Recommended in favor

Strong

Certainty of evidence

Moderate

In outpatient settings, WHO suggests using lateral flow urine lipoarabinomannan assay (LF-LAM) to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: with signs and symptoms of TB (pulmonary and/or extrapulmonary) or seriously ill

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Low

In outpatient settings, WHO suggests using lateral flow urine lipoarabinomannan assay (LF-LAM) to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: irrespective of signs and symptoms of TB and with a CD4 cell count < 100

Status

Maintained

Recommended in favor

Conditional

Certainty of evidence

Very low

In outpatient settings, WHO recommends against using lateral flow urine lipoarabinomannan assay (LF-LAM) to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: without assessing TB symptoms

Status

Maintained

Recommended against

Strong

Certainty of evidence

Very low

In outpatient settings, WHO recommends against using lateral flow urine lipoarabinomannan assay (LF-LAM) to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: without TB symptoms and unknown CD4 cell count, or without TB symptoms and CD4 cell count ≥ 200

Status

Maintained

Recommended against

Strong

Certainty of evidence

Very low

In outpatient settings, WHO recommends against using lateral flow urine lipoarabinomannan assay (LF-LAM) to assist in the diagnosis of active TB in HIV-positive adults, adolescents and children: without TB symptoms and witha CD4 cell count of 100–200

Status

Maintained

Recommended against

Conditional

Certainty of evidence

Very low