Abstract:

Objective

To analyze the correlation between the concentration of lipoarabinomannan（LAM） in sputum and bacterial load and treatment response of pulmonary tuberculosis （PTB）.

Methods

All of 77 patients with PTB treated in our hospital from May 2020 to June 2022 were selected as subjects，45 patients with smear and culture positive PTB smear positive group and 32 patients with smear negative but sputum culture positive PTB smear negative group.Patients with PTB smear positive received standard treatment，and sputum LAM was detected by sandwich enzyme-linked immunosorbent assay before treatment and at 7，14，28，and 56 days after treatment.Sputum LAM＞15 pg/ml was positive.The outcome of the study was 14-day early bactericidal activity （EBA），which was assessed based on mycobacteria growth indicator tube（MGIT） positive detection time （TTD）.

Results

The sensitivity and specificity of sputum LAM were 98.67%and 47.27%，respectively，the positive predictive value and negative predictive value were 71.84% and 96.30%，respectively，the Yodon index was 0.46.Compared with before treatment，sputum LAM decreased on the 14th day of treatment ［（3.74±0.96）log₁₀ pg/ml vs. （2.88±1.00）log₁₀ pg/ml， P＜0.001］.MGIT TTD was significantly prolonged on the 14th day of treatment compared with before treatment ［（133.56±34.63）h vs.（308.69±108.67）h， P＜0.001］.At 14 days of EBA，the EBA represented by MGIT TTD increased （202.42±84.94）h，and the sputum LAM concentration decreased （1.54±0.93）log₁₀ pg/ml.There was high consistency between LAM-ELISA and MGIT in 45 cases before and during treatment.By Pearson correlation analysis，the LAM concentration of log₁₀ transformation in all patients was correlated with MGIT TTD before treatment （r ＝-0.680， P＜0.001），on day 7 （r＝-0.541， P＜0.001），and on day 14 （r＝-0.420， P ＝0.008） and the 28th day （r＝-0.415， P＝0.015） showed a significant negative correlation.6 cases（13.33%） phlegm did not turn negative after intensive treatment.Sputum LAM before treatment was higher in patients without sputum conversion than in patients with sputum conversion ［（4.46±1.05）log₁₀ pg/ml vs. （3.58±0.93）log₁₀ pg/ml，P＝0.040］.The area under the receiver operating characteristic （ROC） curve of LAM before treatment for predicting sputum not turning negative after intensive treatment was 0.872 （95%CI： 0.753-0.991），the sensitivity and specificity were 83.33% and 84.62%，respectively，and the cut-off value was 4.61 log₁₀ pg/ml.

Conclusion

Sputum LAM may be a biomarker of Mycobacterium tuberculosis（MTB）load before treatment and a pharmacodynamic biomarker of bacterial load change during treatment.Sputum LAM may be a useful tool for real-time monitoring of bacterial load and therapeutic response.

Key words: Pulmonary tuberculosis, Lipoarabinomannan, Bacterial load, Therapeutic response