Parallel use of low-complexity automated nucleic acid amplification tests and lateral flow urine lipoarabinomannan assays to detect tuberculosis disease in adults and adolescents living with HIV

Abstract

This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To compare the diagnostic accuracy of parallel use of lateral flow urine lipoarabinomannan on urine and low-complexity automated nucleic acid amplification tests on respiratory samples versus each test alone for detection of tuberculosis disease in adults and adolescents living with HIV who present with presumptive tuberculosis. Secondary objectives To investigate the following sources of heterogeneity: clinical setting; signs and symptoms of tuberculosis; screening positivity for tuberculosis disease by chest x-ray, C-reactive protein elevation, and molecular World Health Organization-recommended rapid diagnostics; seriously ill; advanced HIV; and CD4 cell count.

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Clinical pathway for LC‐aNAATs and LF‐LAM in parallel for diagnosis of tuberculosis among adults and adolescents living with HIV Abbreviations: DR‐TB: drug resistant TB; LAM: lipoarabinomannan; LC‐aNAAT: low‐complexity automated nucleic acid amplification test; LF‐LAM: lateral flow lipoarabinomannan assay; mWRD: molecular World Health Organization‐recommended diagnostics; TB: tuberculosis. Footnotes ^aPeople aged 10 years and above, HIV‐positive, and attending a health facility.
^bSystematic screening for TB disease should be conducted if screening positive for TB signs and symptoms including WHO‐recommended symptom screen (i.e. WHO four‐symptom screen) or signs and symptoms of extrapulmonary TB (or both). Other screening tools that may be used include: C‐reactive protein with a cut‐off of greater than 5 mg/L, chest X‐ray, molecular WHO‐recommended rapid tests. The following populations further qualify for TB testing regardless of TB screening result: inpatients in medical wards where the TB prevalence is greater than 10% (molecular WHO‐recommended rapid tests including LC‐aNAAT should be used); inpatients with advanced HIV disease (CD4 less than 200 cells/mm³ or WHO clinical stage 3 or 4 events) or being seriously ill (respiratory rate greater than 30 breaths/minutes or temperature greater than 39 °C or heart rate greater than 120 beats/minute or unable to walk unaided) (LF‐LAM should be used as an add‐on to clinical judgement in combination with other tests); outpatients who are seriously ill or have a CD4 less than 100 cells/mm³ or a WHO clinical stage 3 or 4 event (LF‐LAM should be used as an add‐on to clinical judgement in combination with other tests).
^cAmongst inpatients, LF‐LAM may assist in the diagnosis of active TB in HIV‐positive adults and adolescents if: signs and symptoms of TB; or advanced HIV disease; or seriously ill. Amongst outpatients, LF‐LAM may assist in the diagnosis of active TB in HIV‐positive adults and adolescents if: signs and symptoms of TB or seriously ill; or CD4 less than 100 cells/mm³; or a WHO clinical stage 3 or 4 event.
^dThe LF‐LAM strip‐test that can detect the LAM antigen in urine at the point‐of‐care. 
^eLC‐aNAATs for TB diagnosis and detection of resistance to isoniazid or rifampicin (or both). LC‐aNAATs evaluated in this review include Xpert MTB/RIF and Xpert MTB/RIF Ultra (Cepheid, Sunnyvale, USA); Truenat MTB and MTB Plus (Molbio Diagnostics, Goa, India); STANDARD M10 (SD Biosensor, Republic of Korea); and IRON‐qPCR (BIONEER, Republic of Korea).
^fPeople testing positive on either LF‐LAM or LC‐aNAAT are recommended to receive tuberculosis treatment.