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Additional studies are needed to examine the predictive value of this novel biomarker on treatment outcomes.CCTV video from inside one of the Cecil Hotel elevators show a clearly agitated Lam jumping in and out of the elevator as if she thinks she’s being followed before she finally exits the elevator and disappears. These results indicate that the LAM-ELISA can determine LAM concentration in sputum, and sputum LAM measured by the assay may be used as a biomarker of bacterial load prior to and during TB treatment. Major limitations of this study include a relatively small number of patients, treatment duration up to only 56 days, lack of quantitative sputum culture CFU count data, and no examination of the correlation of sputum LAM to clinical cure. There was a 1.29 log10 decrease of sputum LAM concentration, corresponding to an increase of 221 hours for MGIT TTD during the first 14 days of treatment, a treatment duration often used in early bactericidal activity (EBA) trials.
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Declines in sputum LAM concentrations correlated with increases of MGIT TTD in individual patients. In a prospective longitudinal cohort study, 40 drug-susceptible pulmonary TB patients (aged 18-69 years 60% male) were enrolled during the first 56 days of the standard 4-drug therapy. Among both LAM and MGIT MTB-culture-positive samples, log10-transformed LAM concentration and MGIT time to detection (TTD) showed a good inverse relationship (r = -0.803, p < 0.0001). The LAM-ELISA detected all smear- and MTB-culture-positive samples (n = 70) and 50% (n = 29) of smear-negative but culture-positive samples (n = 58) (versus 79.3% 46 positive cases by the Xpert MTB/RIF), but none from non-TB patients (n = 56). Some sputum specimens were also examined by Xpert MTB/RIF. In a case-control cohort diagnostic study, sputum specimens were collected from 308 patients (aged 17-69 years 62% male) diagnosed as having pulmonary TB diseases or non-TB diseases, but who could expectorate sputum, and were then evaluated by smear microscopy, BACTEC MGIT 960 Mycobacterial Detection System (MGIT) and Lowenstein-Jensen (LJ) culture, and LAM-ELISA. Two clinical studies were performed between the years 20 in Manila, Philippines, in patients without known human immunodeficiency virus (HIV) coinfection. It detected slow-growing NTMs but without cross-reacting to common oral bacteria. The LAM-ELISA had a lower limit of quantification of 15 pg/mL LAM, corresponding to 121 colony-forming units (CFUs)/mL of MTB strain H37Rv.
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Using these antibodies, a sandwich enzyme-linked immunosorbent assay (LAM-ELISA) was developed to quantitate LAM concentration. Phage display technology was used to isolate monoclonal antibodies binding to epitopes unique in LAM from MTB and slow-growing nontuberculous mycobacteria (NTM). In this report, we evaluated the ability of a novel immunoassay to measure concentrations of LAM in sputum as a biomarker of bacterial load prior to and during treatment in pulmonary tuberculosis (TB) patients. Lipoarabinomannan (LAM) is a major antigen of Mycobacterium tuberculosis (MTB).
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