Diagnostic accuracy of induced sputum LAM ELISA for tuberculosis diagnosis in sputum-scarce patients.
OBJECTIVE
To examine whether a lipoarabinomannan (LAM) enzyme-linked immunosorbent assay (ELISA) that offers diagnostic utility using urine in patients with tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection can be used in induced sputum to diagnose sputum-scarce  patients with suspected TB.


METHODS
LAM was measured in induced sputum samples obtained from 61 consecutively recruited sputum-scarce TB suspects in a tertiary hospital respiratory clinic in South Africa. Liquid culture positivity for Mycobacterium tuberculosis was used as the reference  standard. Receiver operating characteristic analysis was used to assess alternative LAM concentration cut-offs.


RESULTS
A total of 87% (53/61) of study patients had a valid M. tuberculosis culture result; 49% (23/53) were HIV-infected and 17% (9/53) were culture-positive for M.  tuberculosis. Induced sputum smear microscopy and LAM ELISA had an overall sensitivity of 56% (95%CI 27-81); however, the specificity of LAM ELISA was 48% (95%CI 34-62), while the positive and negative predictive values were respectively 18% (95%CI 8-36) and 84% (95%CI  65-94). An optimal rule-in cut-off selected by receiver operating characteristic (LAM concentration >5.73 ng/ml) increased test specificity to 98% and reduced sensitivity to 22%. Normalisation of the assay for sample total protein or cell count did not improve diagnostic accuracy.


CONCLUSIONS
In this proof-of-concept study, the ELISA was not clinically useful for TB diagnosis using induced sputum.
Lung Infection and Immunity Unit, Division of Pulmonology, University of Cape Town Lung Institute and Clinical Immunology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
J G
JG
Peter
T J
TJ
Cashmore
R
R
Meldau
G
G
Theron
R
R
van Zyl-Smit
K
K
Dheda
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D060085:Coinfection; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000453:epidemiology*; D006801:Humans; D008070:Lipopolysaccharides / Q000302:isolation & purification*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013019:South Africa / Q000453:epidemiology; D013183:Sputum / Q000382:microbiology*; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000453:epidemiology / Q000382:microbiology*
D015415:Biomarkers; D008070:Lipopolysaccharides; C050016:lipoarabinomannan