Background
Methods
Setting and patients
Procedures and samples
Laboratory procedures
Clinical outcomes
Data analysis
Diagnostic yield of Determine TB-LAM and relationship with patient symptoms and other characteristics
Diagnostic accuracy of Determine TB-LAM
Patient characterization
Results
Patients enrolled and their characteristics
All patients (n = 427) | Patients with a TB diagnosis (n = 139) | Patients without a TB diagnosis (n = 288) |
P value | |
---|---|---|---|---|
Age (years), median (IQR) | 36.1 (28.9–42.4) | 33.8 (27.2–39.7) | 37.1 (30.0–44.0) | 0.008 |
Female | 259 (60.7) | 90 (64.8) | 169 (58.7) | 0.229 |
New HIV diagnosis on admission | 82 (19.2) | 34 (24.5) | 48 (16.7) | 0.055 |
TB characteristics | ||||
History of previous TB* | 196 (46.1) | 50 (36.2) | 146 (50.9) | 0.005 |
RIF resistance | 4 (0.9) | 4 (2.9) | 0 | 0.004 |
ART status | ||||
ART-naive | 177 (41.5) | 71 (51.1) | 106 (36.8) | 0.019 |
ART interrupted | 71 (16.6) | 19 (13.7) | 52 (18.1) | |
Current ART use | 179 (41.9) | 49 (35.3) | 130 (45.1) | |
Treatment duration if currently on ART (years), median (IQR)a
| 1.6 (0.6–3.6) | 1.3 (0.2–2.9) | 1.7 (0.6–3.7) | 0.157 |
CD4 counts (cells/μL)* | ||||
Median (IQR) | 149 (55–312) | 80 (33–182) | 191 (73–392) | <0.001 |
<50 | 94 (22.2) | 53 (38.4) | 41 (14.3) | |
50–99 | 66 (15.6) | 21 (15.2) | 45 (15.7) | |
100–149 | 54 (12.7) | 19 (13.8) | 35 (12.2) | |
150–199 | 42 (9.9) | 16 (11.6) | 26 (9.1) | |
≥200 | 169 (39.9) | 29 (21.0) | 140 (49.0) | |
HIV viral load (log copies/mL)b
| ||||
Median (IQR) | 4.4 (1.6–5.5) | 5.1 (3.3–5.8) | 4.0 (1.6–5.4) | <0.001 |
Virally suppressed (<400 copies/mL) | 131 (31.6) | 25 (19.8) | 106 (36.8) | 0.001 |
Haemoglobin levels* | ||||
Median (IQR) | 9.6 (7.7–11.6) | 8.4 (6.8–10.2) | 10.2 (8.2–12.2) | <0.001 |
No/mild anaemia | 144 (34.2) | 28 (20.1) | 116 (41.1) | |
Moderate/severe anaemia | 277 (65.8) | 111 (79.9) | 166 (58.9) | |
C-reactive protein (mg/L)c
| ||||
Median (IQR) | 73 (17–153) | 112 (70–182) | 54 (12–135) | <0.001 |
>50 | 246 (61.2) | 108 (82.4) | 138 (50.9) | <0.001 |
Symptoms | ||||
Cough ≥2 weeks* | 34 (8.0) | 18 (13.0) | 16 (5.6) | 0.008 |
Sputum production* | 161 (38.3) | 51 (37.5) | 110 (38.7) | 0.808 |
Current cough* | 201 (47.4) | 84 (60.9) | 117 (40.9) | <0.001 |
Current fever* | 63 (14.9) | 24 (17.5) | 39 (13.6) | 0.294 |
Current night sweats* | 174 (41.0) | 73 (52.9) | 101 (35.3) | 0.001 |
Current reported weight loss* | 189 (44.5) | 76 (55.1) | 113 (39.4) | 0.002 |
Positive WHO symptoms screen* | 389 (91.5) | 134 (97.1) | 255 (88.9) | 0.005 |
Samples tested and laboratory-confirmed TB diagnoses made
Proportion diagnosed by Determine TB-LAM (true positives) | ||||
---|---|---|---|---|
Samples from which TB diagnoses were made | Number of TB diagnoses | Diagnostic yield, % (95% CI) | Number | Proportion, % (95% CI) |
All clinical samples and tests | 139 | 100 | 53 | 38.1 (30.0–46.7) |
Study samples collected during the first 24 h of admission | ||||
Urine | ||||
Urine Xpert (unconcentrated) | 59 | 42.4 (34.1–51.1) | 37 | 62.7 (49.1–75.0) |
Urine Xpert (concentrated) | 82 | 59.0 (50.3–67.3) | 43 | 52.4 (41.1–63.6) |
Sputum | ||||
Smear microscopy | 27 | 19.4 (13.2–27.0) | 15 | 55.6 (35.3–74.5) |
Xpert (1st sample only) | 37 | 26.6 (19.5–34.8) | 17 | 45.9 (29.5–63.1) |
Xpert (either sample) | 39 | 28.1 (20.8–36.3) | 17 | 43.6 (27.8–60.4) |
All study samples collected during any point during admission | ||||
All EPTB cases* | 113 | 81.3 (73.8–87.4) | 51 | 45.1 (35.8–54.8) |
Blood | 41 | 29.5 (22.1–37.8) | 27 | 65.9 (49.4–79.9) |
Pleural fluid | 13 | 9.4 (5.1–15.5) | 4 | 30.8 (9.0–61.4) |
Urinea
| 92 | 66.2 (57.9–74.0) | 46 | 50.0 (39.4–60.6) |
Cerebrospinal fluid | 8 | 5.8 (2.5–11.0) | 1 | 12.5 (0.3–52.7) |
Lymph node fine needle aspirate | 6 | 4.3 (1.6–9.2) | 4 | 66.7 (22.3–95.7) |
Among TB patients by LAM status (n = 139) | ||||
---|---|---|---|---|
LAM-positive (n = 53) | LAM-negative (n = 83) | No LAM result (n = 3) |
P value* | |
Age (years), median (IQR) | 33.4 (25.9–40.6) | 34.2 (28.2–38.7) | 25.3 (25.1–32.4) | 0.582 |
Female | 30 (56.6) | 57 (68.7) | 3 (100) | 0.153 |
New HIV diagnosis on admission | 19 (35.9) | 14 (16.9) | 1 (33.3) | 0.012 |
History of previous TBa
| 17 (32.1) | 31 (37.8) | 2 (66.7) | 0.497 |
ART status | ||||
ART-naive | 28 (52.8) | 42 (50.6) | 1 (33.3) | 0.058 |
ART interrupted | 11 (20.8) | 7 (8.4) | 1 (33.3) | |
Current ART use | 14 (26.4) | 34 (41.0) | 1 (33.3) | |
If currently on ART, treatment duration (years), median (IQR)* | 0.1 (0–2.5) | 1.5 (0.6–4.1) | 0.8 (0.8–0.8) | 0.055 |
CD4 counts (cells/uL)a
| ||||
Median (IQR) cells/μL | 42 (23–91) | 140 (47–247) | 74 (22–546) | <0.001 |
<50 | 30 (56.6) | 22 (26.8) | 1 (33.3) | <0.001 |
50-99 | 11 (20.8) | 9 (11.0) | 1 (33.3) | |
100-149 | 7 (13.2) | 12 (14.6) | 0 | |
150-199 | 4 (7.6) | 12 (14.6) | 0 | |
≥200 | 1 (1.9) | 27 (32.9) | 1 (33.3) | |
HIV viral load (log copies/mL)b
| ||||
Median (IQR) | 5.4 (4.3–6.0) | 4.7 (2.5–5.5) | 4.5 (3.2–5.9) | 0.005 |
Virally suppressed (<400 copies/mL) | 4 (8.0) | 21 (26.6) | 0 | 0.011 |
Anaemia category | ||||
Median (IQR) | 7.6 (6.5–8.6) | 9.0 (7.4–11.1) | 7.1 (6.9–11.8) | <0.001 |
No/mild anaemia | 3 (5.7) | 24 (28.9) | 1 (33.3) | 0.001 |
Moderate/severe anaemia | 50 (94.3) | 59 (71.1) | 2 (66.7) | |
C-reactive protein (mg/L)b
| ||||
Median, (IQR) | 168 (107–204) | 95 (44–142) | 100 (87–134) | <0.001 |
<50 | 0 | 23 (29.5) | 0 | <0.001 |
≥50 | 50 (100) | 55 (70.5) | 3 (100) | |
Symptoms | ||||
Cough ≥2 weeksa
| 8 (13.2) | 11 (13.4) | 0 | 0.972 |
Sputum productiona
| 22 (41.5) | 27 (33.8) | 2 (66.7) | 0.364 |
Current cougha
| 31 (58.5) | 22 (62.2) | 2 (66.7) | 0.667 |
Current fevera
| 22 (41.5) | 27 (33.8) | 2 (66.7) | 0.436 |
Current night sweats | 11 (21.2) | 13 (15.9) | 0 | 0.965 |
Current reported weight lossa
| 30 (56.6) | 44 (53.7) | 2 (66.7) | 0.737 |
Positive WHO symptoms screena
| 52 (98.1) | 79 (96.3) | 3 (100) | 0.553 |
RIF resistance | ||||
Yes | 1 (1.9) | 3 (3.6) | 0 | 1 |
Diagnostic accuracy of Determine TB-LAM urine testing
Comparative diagnostic yield of urine and sputum samples obtained in the first 24 hours
Sub-analysis of patients with CD4 cell counts <100 cells/μL
Relationship between patient characteristics and respiratory symptoms and the diagnostic yield of Determine TB-LAM
Diagnostic yield among patients with pulmonary and extrapulmonary forms of HIV-associated tuberculosis
Comparative diagnostic yield of urine-Xpert and Determine TB-LAM
Comparison of the characteristics and mortality risk of tuberculosis patients with positive (n = 53) or negative (n = 83) urine-lipoarabinomannan status
Unadjusted odds ratio (95% CI) | Log-rank | Adjusted odds ratio (95% CI) | Log-rank | |
---|---|---|---|---|
Age (for each year decrease) | 1.01 (0.98–1.05) | 0.491 | ||
Gender | ||||
Female | 1.00 | 0.154 | ||
Male | 1.68 (0.82–3.43) | |||
ART status | ||||
Any ART exposure | 1.00 | 0.748 | ||
ART naive | 1.12 (0.56–2.24) | |||
History of previous TB | ||||
Yes | 1.0 | 0.496 | ||
No | 1.29 (0.62–2.67) | |||
CD4 category (cells/uL) | ||||
≥150 | 1.00 | <0.001 | 1.00 | 0.002 |
100–149 | 4.55 (1.22–16.98) | 4.37 (1.12–16.98) | ||
50–99 | 9.53 (2.64–34.35) | 6.76 (1.78–25.65) | ||
<50 | 10.64 (3.61–31.36) | 7.20 (2.34–22.17) | ||
Anaemia category | ||||
None/mild | 1.00 | <0.001 | 1.00 | 0.051 |
Moderate | 4.00 (1.03–15.44) | 2.41 (0.57–10.24) | ||
Severe | 9.66 (2.64–35.33) | 4.62 (1.14–18.74) | ||
Self-reported sputum production | ||||
No | 1.00 | 0.264 | ||
Yes | 1.51 (0.73–3.13) | |||
Sputum produced in the first 24 hours | ||||
Yes | 1.00 | 0.841 | ||
No | 1.08 (0.52–2.25) | |||
Sputum sample produced during study admission | ||||
Yes | 1.00 | 0.749 | ||
No | 1.13 (0.54–2.35) | |||
WHO screen positive | ||||
No | 1.00 | 0.541 | ||
Yes | 1.97 (0.20–19.50) |
Unadjusted hazard ratio (95% CI) | Log-rank | Adjusted hazard ratio (95% CI) | Log-rank | |
---|---|---|---|---|
Age (for each year decrease) | 1.01 (0.97–1.06) | 0.545 | ||
Gender | ||||
Female | 1.00 | 0.093 | 1.00 | 0.205 |
Male | 2.17 (0.88–5.35) | 1.80 (0.73–4.48) | ||
ART status | ||||
Current ART | 1.00 | 0.922 | ||
ART naive | 1.18 (0.43–3.24) | |||
Interrupted ART | 1.29 (0.32–5.18) | |||
CD4 category (cells/uL) | ||||
≥150 | 1.00 | 0.261 | ||
199–149 | 3.30 (0.74–14.75) | |||
50–99 | 1.58 (0.26–9.48) | |||
<50 | 2.92 (0.80–10.61) | |||
HIV viral load (log copies/mL) | ||||
<400 | 1.00 | 0.683 | ||
≥400 | 1.30 (0.37–4.48) | |||
C-reactive protein (mg/L) | ||||
<50 | 1.00 | 0.262 | ||
≥50 | 3.16 (0.42–23.47) | |||
LAM-positive | ||||
No | 1.00 | 0.007 | 1.00 | 0.004 |
Yes | 3.56 (1.35–9.36) | 4.20 (1.50–11.75) | ||
RIF-resistant TB | ||||
No | 1.00 | 0.082 | 1.00 | 0.032 |
Yes | 4.90 (1.13–21.24) | 8.41 (1.74–40.67) |