Diagnostic Accuracy of Lateral Flow Urine LAM Assay for TB Screening of Adults with Advanced Immunosuppression Attending Routine HIV Care in South Africa.
BACKGROUND
We assessed the diagnostic accuracy of Determine TB-LAM (LF-LAM) to screen for tuberculosis among ambulatory adults established in HIV care in South Africa.


METHODS
A systematic sample of adults attending for HIV care, regardless of symptomatology, were enrolled in the XPHACTOR study, which tested a novel algorithm for prioritising investigation with Xpert MTB/RIF. In this substudy, restricted to participants with enrolment CD4<200x106/l, urine was stored at enrolment for later testing with LF-LAM. Sputum was sent for immediate Xpert MTB/RIF if any of: current cough, fever ≥3 weeks, body mass index (BMI)<18.5kg/m2, CD4<100x106/l (or <200x106/l if pre-ART), weight loss ≥10% or strong clinical suspicion were present; otherwise, sputum was stored for Xpert testing at study completion. Participants were reviewed monthly, with reinvestigation if indicated, to 3 months, when sputum and blood were taken for mycobacterial culture. We defined tuberculosis as "confirmed" if Xpert, line probe assay or culture for M. tuberculosis within six months of enrolment were positive, and "clinical" if tuberculosis treatment started without microbiological confirmation.


RESULTS
Amongst 424 participants, 61% were female and 57% were taking ART (median duration 22 months); median age, CD4 and BMI were 39 years, 111x106/l, and 23 kg/m2. 56/424 (13%) participants had tuberculosis (40 confirmed, 16 clinical). 24/424 (5.7%) vs. 8/424 (1.9%) were LAM-positive using grade 1 vs. grade 2 cut-off. Using grade 1 cut-off, sensitivity for confirmed TB (all clinical TB excluded) was 12.5% (95% CI 4.2%, 26.8%) and in CD4<100x106/l vs. CD4 ≥100x106/l was 16.7% (95% CI 4.7%, 37.4%) vs. 6.3% (95% CI 0.2%, 30.2%). Specificity was >95% irrespective of diagnostic reference standard, CD4 stratum, or whether grade 1 or grade 2 cut-off was used.


CONCLUSIONS
Sensitivity of LF-LAM is too low to recommend as part of intensified case finding in ambulatory patients established in HIV care.
London School of Hygiene & Tropical Medicine, London, United Kingdom.
Yasmeen
Y
Hanifa
London School of Hygiene & Tropical Medicine, London, United Kingdom.
Katherine L
KL
Fielding
Aurum Institute, Johannesburg, South Africa.|University of the Witwatersrand, Johannesburg, South Africa.
Violet N
VN
Chihota
Mamelodi Hospital, Pretoria, South Africa.
Lungiswa
L
Adonis
Aurum Institute, Johannesburg, South Africa.|University of the Witwatersrand, Johannesburg, South Africa.
Salome
S
Charalambous
University of the Witwatersrand, Johannesburg, South Africa.|Department of Medicine, Chris Hani Baragwanath Hospital, Johannesburg, South Africa.
Alan
A
Karstaedt
Aurum Institute, Johannesburg, South Africa.
Kerrigan
K
McCarthy
National Health Laboratory Service, Johannesburg, South Africa.|University of Cape Town, Cape Town, South Africa.
Mark P
MP
Nicol
Aurum Institute, Johannesburg, South Africa.
Nontobeko T
NT
Ndlovu
University of the Witwatersrand, Johannesburg, South Africa.|Department of Medicine, Chris Hani Baragwanath Hospital, Johannesburg, South Africa.
Faieza
F
Sahid
London School of Hygiene & Tropical Medicine, London, United Kingdom.|Aurum Institute, Johannesburg, South Africa.|University of the Witwatersrand, Johannesburg, South Africa.|Advancing Care and Treatment (ACT) for TB/HIV, South African Medical Research Council Collaborating Centre for HIV and TB, Cape Town, South Africa.
Gavin J
GJ
Churchyard
London School of Hygiene & Tropical Medicine, London, United Kingdom.|University of the Witwatersrand, Johannesburg, South Africa.
Alison D
AD
Grant
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008070:Lipopolysaccharides / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D019095:Point-of-Care Systems; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D013019:South Africa; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000378:metabolism
D044966:Anti-Retroviral Agents; D008070:Lipopolysaccharides; C050016:lipoarabinomannan