Supplemental Digital Content 1

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Supplemental Digital Content 1:

Figure. Study flow diagram

556 patients screened

Not enrolled n=129 HIV negative / test refused (n=40)

Research process related problems (n=22) Refused participation (n=21)

On TB treatment (n=19)

>24hours in EC (n=13)

Discharged or transferred before study procedures (n=9)

Mainly neurological / trauma / gynaecological / psychiatric presentation (n= 4)

Pregnant (n=1)

427 enrolled

Not analyzed (n=16) TB workup limited to microscopy (n=10) No urine obtained (n=3)

HIV confirmation test negative (n=2) Died before specimens taken (n=1)

411 included in analysis

170 (41.4%) Mtb positive 241 (58.6%) Mtb negative

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Table. Results of confirmatory testing in participants with confirmed TB

Number of participants with confirmed TB

Xpert test positive

^a

Only Xpert test positive

Xpert and culture

(any site) tests positive

Xpert and blood culture

tests positive

Only culture

test positive

(any site)

Only blood culture

test positive

Culture test positive

(any site)

Culture test positive

(blood)

All (n=170)

125 32 93 44 45 19 138 63

Laboratory LAM positive (n=71)

54 12 42 28 18 9 59 37

Point-of-care LAM positive (n=71)

55 12 43 29 16 10 59 39

a: Only sputum positive n=61, Sputum and extra-pulmonary samples positive n=27, Only extra-

pulmonary samples positive n=37

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Supplemental Digital Content 3:

Table. Demographic and clinical characteristics of study population

Characteristics at enrollment, n (%) unless otherwise specified

n All

(n = 411)

Mtb*

confirmed (n = 170)

Mtb not confirmed

(n = 241)

p- value^†

Demographics

Age (years) (Median (IQR)) 41

1

35 (30-43) 35 (25-42) 36 (31-44) 0.13

Male 41

1 171 (41.6%) 71 (41.8%) 100 (41.5%) 0.96

Clinical history

Current cough of any duration 41

1 350 (85.2%) 147 (86.5%) 203 (84.2%) 0.53

Weight loss within last month 41

1 352 (85.6%) 154 (90.6%) 198 (82.2%) 0.02^†

Night sweats within last month 41

1 218 (53.0%) 102 (60.0%) 116 (48.1%) 0.02^†

Fever within last month 41

1

200 (48.7%) 75 (44.1%) 125 (51.9%) 0.12

Previous TB (any time) 40

9

214 (52.3%) 71 (41.8%) 143 (59.8%) <0.01^†

Previous TB ≤ 2 years 40

9 75 (18.3%) 27 (15.9%) 48 (20.1%) 0.28

Antiretroviral therapy naïve 41

1 123 (29.9%) 58 (34.1%) 65 (27.0%) 0.12

Currently on antiretroviral therapy 41

1 194 (47.2%) 71 (41.8%) 123 (51.0%) 0.06

Defaulted antiretroviral therapy 41

1

88 (21.4%) 41 (24.1%) 47 (19.5%) 0.26

Unknown if on antiretroviral therapy 41 1

6 (1.5%) 0 (0.0%) 6 (2.5%) 0.44

First line antiretroviral regime 41

1 162 (39.4%) 53 (31.2%) 109 (45.2%) <0.01^† Second line antiretroviral regime 41

1 47 (11.4%) 13 (7.6%) 34 (14.1%) 0.04^†

Unknown antiretroviral regime 41

1 79 (19.2%) 46 (27.1%) 33 (13.7%) <0.01^† Clinical findings

Height (centimeter) (Median (IQR^‡)) 37

9 163 (157-

169) 163 (157-167) 163 (157-170) 0.25

Weight (kilogram) (Median (IQR)) 38

0

54 (46-65) 53 (46-61) 55 (47-67) 0.13

Body Mass Index (kg/m²) (Median (IQR)) 37 9

20 (17-24) 20 (17-24) 20 (18-25) 0.38

Underweight (Body Mass Index < 18.5 kg/m²) 37 9

136 (35.9%) 60 (37.7%) 76 (34.5%) 0.52

Temperature (centigrade) (Median (IQR)) 40

8 36.8 (36.1-

37.8) 36.8 (36.1-

38.0) 36.7 (36.2-37.8) 0.63 Systolic blood pressure (mmHg) (Median (IQR)) 41

1 111 (98-125) 111 (99-123) 111 (97-127) 0.81 Diastolic blood pressure (mmHg) (Median

(IQR))

41 1

71 (61-81) 72 (60-80) 71 (61-82) 0.98

Heart rate (beats per minute) (Mean ± SD) 41 1

122 ± 22 126 ± 23 119 ± 21 0.01^†

Respiratory rate (breaths per minute) (Median (IQR))

40 8

24 (19-30) 24 (18-30) 24 (20-32) 0.11

Oxygen saturation level (Median (IQR)) 40

3 97 (94-99) 98 (95-99) 96 (93-99) 0.08

Hemoglobin (g/dl) (Mean ± SD^§) 40

7 9.7 ± 2.6 9.0 ± 2.4 10.3 ± 2.7 <0.01^† Mean corpuscular volume (fL^¶) (Mean ± SD) 40

4

86.7 ± 9.0 84.8 ± 8.1 87.9 ± 9.3 <0.01^† White blood cell count (x 10⁹/l) (Median (IQR)) 40

9

8.4 (5.8- 13.6)

7.5 (5.4-12.6) 9.1 (6.3-14.7) <0.01^†

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CD4 cell count (cells/µL) (Median (IQR)) 40 5

87 (30-218) 65 (23-154) 121 (37-268) <0.01^†

Mtb = Mycobacterium tuberculosis*;

†

Indicates statistical significance;

‡

IQR= Interquartile range;

§

SD = Standard Deviation;

¶

Femtoliter

Normality were assessed visually (using histograms and Q-Q plots) and with the Shapiro-Wilks test.

Homogeneity of variance were determined with Levene’s test. For continuous data, the Mann-Whitney U test

(non-parametric distribution) or the Independent t-test (parametric distribution) were used. Pearson’s chi-squared

test or Fischer’s exact test were used for categorical data. A significance level of .05 was applied.

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Supplemental Digital Content 4:

Table. Reasons for initiating TB treatment in participants without confirmed TB (n=63) in relation to point-of-care LAM results

Point-of-care LAM positive

^a

(n = 16)

^b

Point-of-care LAM negative (n = 47)

^c

Reason for initiating TB treatment n Reason for initiating TB treatment n

Only LAM positive 7 Suggestive abdominal ultrasound 2

0 Suggestive chest x-Ray 4 Suggestive chest X-Ray 8

Suggestive abdominal ultrasound 3 Suggestive abdominal ultrasound &

suggestive chest X-Ray 6

Raised adenosine deaminase in effusion

fluid

^d

1 Suggestive lumbar puncture or suggestive

computer tomography of the brain 4 Caseous necrosis on microscopic

examination 1 Not improving on antimicrobial agents 4

Raised adenosine deaminase in effusion

fluid

^d

3 Suggestive computer tomography of the

abdomen 1

Suggestive chest x-ray & raised adenosine deaminase in effusion fluid

^d

1 a: Positive LAM defined as grade 1 or higher b: Laboratory LAM negative n=6

c: Laboratory LAM positive n=6

d: Defined as adenosine deaminase > 30 U/L

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Table. Comparison of diagnostic accuracy of lipoarabinomannan (LAM) between point-of-care and laboratory testing on urine samples (missing, invalid and inconclusive results excluded)

Point-of-Care

^*

Laboratory

^†

Sensitivity, % (95%CI

^‡

)

Overall 41.8 (34.3 to 49.

6) 44.1 (36.3 to 52.1)

CD4 ≤ 100 cells/µL 55.1 (45.2 to 64.8) 59.8 (49.6 to

69.4) Specificity, % (95%CI)

Overall 90.5 (86.0 to 93.9) 87.4 (82.5 to

91.3)

CD4 ≤ 100 cells/µL 86.5 (78.7 to 92.2) 83.5 (75.2 to

89.9) Positive Predictive Value, % (95%CI)

Overall 75.5 (66.8 to 82.6) 70.3 (61.9 to

77.5)

CD4 ≤ 100 cells/µL 79.7 (70.5 to 86.7) 77.2 (68.3 to

84.2) Negative Predictive Value, %

(95%CI)

Overall 68.8 (65.8 to 71.6) 69.8 (66.7 to

72.8)

CD4 ≤ 100 cells/µL 66.7 (61.6 to 71.4) 68.9 (63.3 to

74.0) Positive Likelihood Ratio, (95%CI)

Overall 4.4 (2.9 to 6.7) 3.5 (2.4 to 5.1)

CD4 ≤ 100 cells/µL 4.1 (2.8 to 6.7) 3.6 (2.3 to 5.7)

Negative Likelihood Ratio, (95%CI)

Overall 0.6 (0.6 to 0.7) 0.6 (0.6 to 0.7)

CD4 ≤ 100 cells/µL 0.5 (0.4 to 0.7) 0.5 (0.4 to 0.6)

*Overall n=411, CD4≤100 cells/µL n =218;

†Overall n=399, CD4≤100 cells/µL n=211;

‡Confidence interval;

Excluded results: missing (n=1), inconclusive (n=10), and invalid (n=1)

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Supplemental Digital Content 6:

Table. Level of agreement of lipoarabinomannan (LAM) readings (positive or negative) between point-of-care reading and laboratory reading (missing, invalid, and inconclusive results excluded)

Laboratory reading, n(%)

Point-of-care reading, n(%) Negative Positive

^*

Inconclusive

Negative

275 (67.1) 32 (7.8) 8 (2.0)

315 (77)

Positive

23 (5.6) 69 (16.8) 2 (0.5)

94 (23)

Inconclusive *

0 (0.0) 0 (0.0) 0 (0.0)

0 (0.0)

298 (72.7) 101 (24.6) 10 (2.4) 409 (100)

*Urine lipoarabinomannan (LAM) grade-1 cut off or higher

Urine not done by laboratory (n=1) and invalid laboratory results (n=1) excluded;

Shaded areas represent agreement

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Table. Level of agreement of lipoarabinomannan (LAM) readings between point-of-care reading and laboratory reading on urine samples relating to difference in grades (inconclusive results regarded as negative)

Point-of-care reading, n(%)

Laboratory reading, n(%)

0^* 1+ 2+ 3+ 4+

0 283 (69.2) 32 (7.8) 0 (0.0) 0 (0.0) 0 (0.0) 315 (77.0)

1+ 23 (5.6) 24 (5.9) 7 (1.7) 3 (0.7) 0 (0.0) 57 (13.9)

2+ 2 (0.5) 6 (1.5) 4 (1.0) 4 (1.0) 0 (0.0) 16 (3.9)

3+ 0 (0.0) 4 (1.0) 7 (1.7) 7 (1.7) 1 (0.2) 19 (4.6)

4+ 0 (0.0) 0 (0.0) 1 (0.2) 0 (0.0) 1 (0.2) 2 (0.5)

308 (75.3) 66 (16.1) 19 (4.6) 14 (3.4) 2 (0.5) 409 (100)

*Includes inconclusive (n=10) results

Urine not done by laboratory (n=1) and invalid laboratory result (n=1) excluded;

Table. Level of agreement of lipoarabinomannan (LAM) readings between point-of-care reading and laboratory reading on urine samples relating to difference in grades

(missing, invalid, and inconclusive results excluded)

Point-of-care reading, n(%)

Laboratory reading, n(%)

0 1+ 2+ 3+ 4+ Inconclusive*

0 275 (67.1) 32 (7.8) 0 (0.0) 0 (0.0) 0 (0.0) 8 (2.0) 315 (77.0)

1+ 21 (5.1) 24 (5.9) 7 (1.7) 3 (0.7) 0 (0.0) 2 (0.5) 57 (13.9)

2+ 2 (0.5) 6 (1.5) 4 (1.0) 4 (1.0) 0 (0.0) 0 (0.0) 16 (3.9)

3+ 0 (0.0) 4 (1.0) 7 (1.7) 7 (1.7) 1 (0.2) 0 (0.0) 19 (4.6)

4+ 0 (0.0) 0 (0.0) 1 (0.2) 0 (0.0) 1 (0.2) 0 (0.0) 2 (0.5)

Inconclusive* 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)

298 (72.9) 66 (16.1) 19 (4.6) 14 (3.4) 2 (0.5) 10 (2.4) 409 (100) Urine not done by laboratory (n=1) and invalid (n=1) results excluded;

Supplemental Digital Content 1