Diagnostic accuracy, incremental yield and prognostic value of Determine TB-LAM for routine diagnostic testing for tuberculosis in HIV-infected patients requiring acute hospital admission in South Africa: a prospective cohort.
We previously reported that one-third of HIV-positive adults requiring medical admission to a South African district hospital had laboratory-confirmed tuberculosis (TB) and that almost two-thirds of cases could be rapidly diagnosed using Xpert MTB/RIF-testing of concentrated urine samples obtained on the first day of admission. Implementation of urine-based, routine, point-of-care TB screening is an attractive intervention that might be facilitated by use of a simple, low-cost diagnostic tool, such as the Determine TB-LAM lateral-flow rapid test for HIV-associated TB.



Sputum, urine and blood samples were systematically obtained from unselected HIV-positive adults within 24 hours of admission to a South African township hospital. Additional clinical samples were obtained during hospitalization as clinically indicated. TB was defined by the detection of Mycobacterium tuberculosis in any sample using Xpert MTB/RIF or liquid culture. The diagnostic yield, accuracy and prognostic value of urine-lipoarabinomannan (LAM) testing were determined, but urine-LAM results did not inform treatment decisions.



Consecutive HIV-positive adult acute medical admissions not already receiving TB treatment (n = 427) were enrolled regardless of clinical presentation or symptoms. TB was diagnosed in 139 patients (TB prevalence 32.6%; median CD4 count 80 cells/μL). In the first 24 hours of admission, sputum (spot and/or induced) samples were obtained from 37.0% of patients and urine samples from 99.5% of patients (P < 0.001). The diagnostic yields from these specimens were 19.4% (n = 27/139) for sputum-microscopy, 26.6% (n = 37/139) for sputum-Xpert, 38.1% (n = 53/139) for urine-LAM and 52.5% (n = 73/139) for sputum-Xpert/urine-LAM combined (P < 0.01). Corresponding yields among patients with CD4 counts <100 cells/μL were 18.9%, 24.3%, 55.4% and 63.5%, respectively (P < 0.01). The diagnostic yield of urine-LAM was unrelated to respiratory symptoms, and LAM assay specificity (using a grade-2 cut-off) was 98.9% (274/277; 95% confidence interval [CI] 96.9-99.8). Among TB cases, positive urine-LAM status was strongly associated with mortality at 90 days (adjusted hazard ratio 4.20; 95% CI 1.50-11.75).



Routine testing for TB in newly admitted HIV-positive adults using Determine TB-LAM to test urine provides major incremental diagnostic yield with very high specificity when used in combination with sputum testing and has important utility among those without respiratory TB symptoms and/or unable to produce sputum. The assay also rapidly identifies individuals with a poor prognosis.
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.|The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.|Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Stephen D
SD
Lawn
Department of Medicine, University of California San Francisco School of Medicine, San Francisco, CA, USA.
Andrew D
AD
Kerkhoff
Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.|GF Jooste Hospital, Manenberg, Cape Town, South Africa.|Khayelitsha District Hospital, Cape Town, South Africa.
Rosie
R
Burton
Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.|GF Jooste Hospital, Manenberg, Cape Town, South Africa.|Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Charlotte
C
Schutz
School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Andrew
A
Boulle
The Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Monica
M
Vogt
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Ankur
A
Gupta-Wright
Division of Medical Microbiology and Institute for Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.|National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa.
Mark P
MP
Nicol
Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. graemein@mweb.co.za.|GF Jooste Hospital, Manenberg, Cape Town, South Africa. graemein@mweb.co.za.|Khayelitsha District Hospital, Cape Town, South Africa. graemein@mweb.co.za.|Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. graemein@mweb.co.za.
Graeme
G
Meintjes
D000328:Adult; D003955:Diagnostic Tests, Routine / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D008070:Lipopolysaccharides / Q000032:analysis / Q000652:urine; D008297:Male; D000067716:Point-of-Care Testing; D011237:Predictive Value of Tests; D015995:Prevalence; D011379:Prognosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D013019:South Africa / Q000453:epidemiology; D014376:Tuberculosis / Q000175:diagnosis / Q000453:epidemiology; D016482:Urinalysis / Q000379:methods*
D008070:Lipopolysaccharides; C050016:lipoarabinomannan
Africa; Determine TB-LAM; Diagnosis; HIV; Hospital; LAM; Lipoarabinomannan; Screening; Tuberculosis; Urine; Xpert