Remarks

• This recommendation prioritizes concurrent testing over the use of molecular testing andLF-LAM in isolation for diagnosis of TB in children with HIV.
• Use of LC-aNAATs on isolated specimens was also evaluated. The findings supported theuse of LC-aNAATs for initial diagnostic testing for TB in HIV-positive children with signs orsymptoms or who screen positive for pulmonary TB, using sputum, gastric aspirate, stool ornasopharyngeal aspirate, rather than smear or culture.
• This recommendation is conditional because the findings indicate moderate undesirableeffects (i.e. decreased specificity, resulting in more false positive test results) when comparedwith a single test strategy.
• The product for which eligible data met the LC-aNAAT class-based performance criteriafor this recommendation was Xpert MTB/RIF Ultra. The performance of Truenat MTB Plusand MTB-RIF Dx for this recommendation could not be assessed, as data were unavailable.

Implementation considerations

• Global and national HIV and TB programmes need to communicate regularly and clearly, indicating responsibilities for concurrent testing for people living with HIV.
• Concurrent testing maximizes diagnostic opportunity and accuracy of case detection, is a more efficient way to address the needs of this population and is preferred even if the testing workload may increase.
• A positive result on either test is sufficient to confirm TB diagnosis.
• Patient loss to follow-up for the second test result should be monitored and prevented. Patients should be provided with information to understand the concurrent testing approach and the need for follow-up.
• Testing capacity should be secured for the second test, as volumes will increase.
• Adequate staffing capacity and training are needed to improve the collection of different sample types and laboratory processing of collected samples.
• Performing the same test on a new sample may need additional regulatory approval on a national and international level.
• Infrastructure and training on how to collect a stool sample privately should be available.
• As with all WHO-recommended TB diagnostics, quality assurance programmes for both sample types are required.
• At a primary health care level, in a situation of sputum paucity or absence, stool and nasopharyngeal aspirate may be feasible, whereas collection of more invasive specimen types (i.e. induced sputum, BAL and gastric aspirate) would require upward referral, depending local capacity and expertise. In these circumstances, performing stool testing at primary health care level and waiting for a test result before upward referral of the child may be appropriate.
• The LF-LAM performed in point-of-care settings may be the first positive result and is sufficient to make the initial diagnosis. A respiratory sample is still required for rifampicinresistance detection, and is also required when the LF-LAM result is negative.
• Where LF-LAM is not available for testing of people living with HIV, efforts should be made to ensure access to testing.
• LF-LAM does not differentiate Mtb from other mycobacterial species. However, the LAM antigen detected in a clinical sample in TB endemic areas is most likely attributable to Mtb.
• When LF-LAM results are consistently positive, without positive LC-aNAAT results, investigation of the quality of testing and local epidemiology of non-tuberculosis mycobacteria and extrapulmonary TB in the tested population is warranted to understand the difference.
• Interpreting bands on the LF-LAM test strip should be performed using the manufacturer’s reading card to minimize incorrect results.
• LF-LAM test strips must be stored according to the manufacturer’s instructions (e.g. between 2 and 30 °C) in sealed bags and not used after expiration.
• Infrastructure to collect a urine sample privately should be available. Patients should be instructed how to properly and sanitarily collect a urine sample to minimize contamination and prevent false positive results.
• Trained staff will be required to perform the LF-LAM test at the point of care.
• As with all WHO-recommended TB diagnostics, quality assurance programmes and quality controls for both tests are required.
• LF-LAM is designed to detect mycobacterial LAM antigen in human urine. Other samples (e.g. sputum, serum, plasma, CSF and other body fluids) or pooled urine specimens should not be used.