Professional Documents
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29722974
0095-1137/10/$12.00 doi:10.1128/JCM.00363-10
Copyright 2010, American Society for Microbiology. All Rights Reserved.
Urinary lipoarabinomannan (LAM) detection is a promising approach for rapid diagnosis of active tuberculosis (TB). In microbiologically confirmed TB patients, quantitative LAM detection results increased progressively with bacillary burden and immunosuppression. Patients with disseminated TB and/or advanced HIV
are target populations for whom urine LAM detection may be particularly useful.
cohort study at three hospitals in South Africa to evaluate the
diagnostic accuracy of the urine LAM test. Hospitalized adult
TB suspects were enrolled after informed consent. Study-directed testing included sputum smear microscopy for acid-fast
bacilli (AFB), sputum mycobacterial culture, mycobacterial
blood cultures, HIV and CD4 testing, urine LAM testing using
the Clearview TB ELISA kit, and additional mycobacterial
cultures (e.g., from enlarged lymph nodes) when clinically indicated. Participants had a follow-up study visit at 2 months.
Participants with at least one positive AFB smear or mycobacterial culture positive for Mycobacterium tuberculosis were determined to have confirmed TB and were included in the
current analysis. Individuals with M. tuberculosis isolated from
a blood culture (mycobacteremia) were considered to have
disseminated disease. Pulmonary TB (PTB) was defined as the
presence of one or more sputa positive for AFB by microscopy
and/or positive for M. tuberculosis by culture. Localized extrapulmonary TB was defined as isolation of M. tuberculosis
from pleural culture or fine-needle aspiration of a lymph node
but not from other respiratory specimens or blood. Quantitative urine LAM test results were expressed as optical density
(OD) readings. The final sample OD was determined by subtracting the OD of the negative control from the sample reading, with a minimum value of 0 (i.e., a value of 0 was reported
if the OD of the negative control was greater than the OD of
the sample). An OD above 0.1 was considered positive per
manufacturer specifications. Multiple linear regression models
were used to determine predictors of higher quantitative urine
LAM test results. Wilcoxon rank sum and Kruskal-Wallis tests
were used to compare nonnormal continuous outcomes; chisquare (2) tests were used to compare categorical outcomes.
A P value of 0.05 was considered statistically significant, and
95% confidence intervals (95% CI) were used. Statistical calculations were performed using Stata 10.1 (StataCorp). This
study was approved by the institutional review boards of Johns
Hopkins University School of Medicine and the University of
Witwatersrand.
Full characteristics of the study population are published
elsewhere (16). Overall, 499 participants were enrolled, and
193 (39%) had confirmed TB (185 with positive cultures for M.
NOTES
OD median
(IQR)
OD mean
(SD)
Localized extrapulmonary
TB (5)a
Pulmonary TB only (145)b
Mycobacteremia only (18)c
Pulmonary TB with
mycobacteremia (25)
P value
0.01 (0.010.06)
0.09 (0.16)
1 (20, 172)
0.13 (0.020.70)
0.64 (0.141.43)
1.4 (0.432.8)
0.63 (0.97)
0.99 (1.02)
1.6 (1.1)
78 (54, 4562)
14 (78, 5294)
21 (84, 6496)
0.0001d
0.003f
2973
OD median
(IQR)
OD mean
(SD)
Negative (88)
0.13 (0.020.62)a,b
0.60 (0.93)
47 (53, 0.420.64)
Positive
Any grade (73)
Grade 1 (13)
Grade 2 (15)
Grade 3 (45)
0.33 (0.0521.71)b
0.18 (0.11.3)a
0.26 (0.032.8)a
0.38 (0.0481.8)a
0.94 (1.15)
0.68 (0.89)
1.13 (1.3)
0.95 (1.18)
47 (64, 0.520.75)
10 (77, 0.460.94)
10 (67, 0.380.88)
27 (60, 0.440.74)
Sputum AFB
smear microscopy
status (no. of
cases)c
a
P 0.18 for comparison of AFB-negative, AFB 1, AFB 2, and AFB 3
results by the Kruskal-Wallis test.
b
P 0.03 for comparison of AFB-negative and AFB-positive results by the
Wilcoxon rank sum test.
c
Grading per WHO guidelines (http://wwwn.cdc.gov/dls/ila/documents/lstc2
.pdf).
(P 0.0001) (Table 3). The median OD increased progressively from 0.10 (IQR, 0.02 to 0.5) to 0.20 (IQR, 0.03 to 0.8) to
0.42 (IQR, 0.04 to 1.0) to 1.3 (IQR, 0.2 to 2.8) in those with
CD4 counts of 150, 101 to 150, 50 to 100, and 50, respectively (P 0.0001).
Multiple linear regression models were used to further explore factors associated with higher quantitative urine LAM
test results. Covariates included in the models were age, sex,
HIV status, mortality at 2 months, TB treatment, mycobacteremia, sputum smear positivity, fever, Karnofsky score, chest X
ray (CXR) cavitation, hypoxia, pulse, and CD4 strata. Adjusting for all other factors, individuals with mycobacteremia had
an average OD that was 0.64 OD units higher than that for
individuals with negative blood cultures (P 0.002); individuals with smear-positive pulmonary TB had an average OD
that was 0.33 OD units higher than that for individuals with
smear-negative pulmonary TB (P 0.05). Among HIV-infected patients, individuals with CD4 counts of 50 had an
average OD that was 1.05 OD units higher than that for individuals with CD4 counts of 150 (P 0.0001). No other
covariates were significantly associated with higher quantitative urine LAM test results.
Taken together, our findings show that quantitative urine
LAM test results correlate with degree of bacillary burden in
patients with microbiologically confirmed TB. Further, the absolute urine LAM test OD increased dramatically as immuno-
OD median
(IQR)
OD mean
(SD)
150 (63)
101150 (16)
50100 (28)
50 (60)
P value
0.10 (0.020.5)
0.2 (0.030.8)
0.42 (0.041.0)
1.3 (0.22.8)
0.0001a
0.42 (0.72)
0.65 (0.96)
0.72 (0.9)
1.4 (1.12)
b
32 (51, 0.380.64)
9 (56, 0.300.80)
20 (71, 0.510.87)
51 (85, 0.730.93)
0.00c
2974
NOTES
J. CLIN. MICROBIOL.
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16.
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