Diagnosis of pleural tuberculosis by multi-targeted loop-mediated isothermal amplification assay based on SYBR Green I reaction: comparison with GeneXpert® MTB/RIF assay

Expert Rev Respir Med. 2023 Jul-Dec;17(11):1079-1089. doi: 10.1080/17476348.2023.2292738. Epub 2023 Dec 26.

Abstract

Background: Diagnosis of pleural tuberculosis (TB) is tedious owing to its close resemblance with malignant pleural effusion and sparse bacterial load in clinical specimens. There is an immediate need to design a rapid and dependable diagnostic test to prevent unnecessary morbidity/mortality.

Research design and methods: A multi-targeted loop-mediated isothermal amplification (MT-LAMP) was deliberated using mpt64 and IS6110 to diagnose pleural TB within pleural fluids/biopsies. MT-LAMP products were analyzed by gel-based and visual detection methods, viz. SYBR Green I, SYBR Green I+deoxyuridine triphosphate uracil-N-glycosylase (dUTP-UNG), and dry methyl green reactions.

Results: In a pilot study, while assessing pleural TB/non-TB control subjects (n = 40), both SYBR Green I+dUTP-UNG/gel-based MT-LAMP assays exhibited better sensitivity/specificity than SYBR Green I and dry methyl green MT-LAMP. Since it is facile to work with SYBR Green I+dUTP-UNG than gel-based MT-LAMP, we validated the performance of SYBR Green I+dUTP-UNG in a higher number of specimens (n = 97), which revealed somewhat higher sensitivity (85.2 vs. 81.5%) and specificity (97.7 vs. 90.7%) than SYBR Green I MT-LAMP. Furthermore, the sensitivity attained by SYBR Green I+dUTP-UNG MT-LAMP was significantly higher (p < 0.001) than GeneXpert.

Conclusions: Our SYBR Green I+dUTP-UNG MT-LAMP is a simple and reliable method to diagnose pleural TB, which may translate into a point-of-care test.

Keywords: Diagnosis; GeneXpert; Mtb; SYBR Green I; SYBR Green I+dUTP-UNG assay; dry methyl green; multi-targeted LAMP; pleural TB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Methyl Green
  • Molecular Diagnostic Techniques
  • Mycobacterium tuberculosis* / genetics
  • Nucleic Acid Amplification Techniques
  • Pilot Projects
  • Sensitivity and Specificity
  • Tuberculosis, Pleural* / diagnosis

Substances

  • SYBR Green I
  • Methyl Green

Supplementary concepts

  • LAMP assay