Detection of LAM in Non-Sputum Specimens Achieves High Accuracy for TB Diagnosis, reveals study
Lipoarabinomannan (LAM) can be detected in non-sputum samples, such as urine, plasma, and serum, in the diagnosis of pulmonary tuberculosis (TB) among patients with HIV. TB is primarily caused by a bacterium known as Mycobacterium tuberculosis, of which sputum is the most common sample taken. A recent study was published in the journal The Lancet eBioMedicine by Paul K. and colleagues.
Tuberculosis continues to be one of the significant challenges globally and remains one of the most serious global health concerns, predominantly in areas of high prevalence rates for HIV. Sputum samples are the most common presentation of TB, though often less easily obtained, especially in HIV patients or non-productors. A simple detection product for LAM - a cell wall component of Mycobacterium tuberculosis can be screened from all other bodily fluids, providing alternative methods for diagnosis.
This was a prospective diagnostic research conducted on adult patients presenting with TB symptoms in South Africa. A total of 684 participants were enrolled, and 210 participants were randomly selected for comprehensive testing, with a case-to-control ratio of 2:1. Concentrations of LAM were detected in time-matched urine, plasma, and serum samples using an electrochemiluminescence immunoassay that used two capture antibodies: FIND 28 and S4–20, to measure the concentration of LAM. The diagnostic performance was assessed by comparing the concentrations of LAM with microbiological reference standards.
• 41% of the TB-positive participants were female with the co-infection of HIV.
• In TB-positive adults, the median urine LAM concentration was 137 pg/mL using FIND 28 and 52 pg/mL using S4–20.
• LAM levels were the highest among HIV-positive participants with CD4+ T cell counts less than 200 cells/mm³.
• Urine LAM had a sensitivity of 62% (95% CI: 53–70%) with a specificity of 99% (95% CI: 96–100%) for the S4–20 antibody.
• In contrast, the sensitivity of plasma and serum LAM levels measured by FIND 28 was 70% (95% CI: 62–78%), with specificities of 90% (95% CI: 82–97%) for plasma and 94% (95% CI: 88–99%) for serum.
• The mean concentration of the average LAM in HIV-positive participants with CD4+ T cell counts below 200 cells/mm³ was significantly higher, indicating that the subgroup performed better in the diagnostics.
• The diagnostic sensitivity of urine LAM (S4–20) was more in the non-HIV participants at 41 % (95 % CI: 24 %–61 %) when compared to 20 % (95 % CI: 8 %–39 %) in HIV-positive participants whose CD4 counts ≥200 cells/mm³.
It was thus concluded that LAM could be identified in specimens other than sputum to help diagnose pulmonary TB, especially among HIV-positive individuals with low CD4+ T cell counts. Further work is required in order to enhance the sensitivity in broader populations. LAM testing both in urine and blood samples can represent an important contribution towards TB diagnostics, especially in areas where availability of sputum samples is challenging.
Reference:
Drain, P. K., Niu, X., Shapiro, A. E., Magcaba, Z. P., Ngcobo, Z., Ngwane, M. W., Thomas, K. K., Dalmat, R. R., Morton, J. F., Budiawan, E., Pinter, A., Cantera, J., Anderson, C., Buchmann, R., Wilson, D., & Grant, B. (2024). Real-world diagnostic accuracy of lipoarabinomannan in three non-sputum biospecimens for pulmonary tuberculosis disease. EBioMedicine, 108(105353), 105353. https://doi.org/10.1016/j.ebiom.2024.105353
