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GeneXpert Ultra in Urine Samples for Diagnosis of Extra-Pulmonary Tuberculosis

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Abstract

Extra-pulmonary tuberculosis (EPTB) continues to be difficult to diagnose. Novel biomarkers in biological specimens offer promise. Detection of Mycobacterium tuberculosis (Mtb) DNA in urine could prove useful in diagnosis of EPTB, possibly due to disseminated disease or micro-abscesses reported in kidneys. The current study was designed to detect Mtb DNA in stored urine samples from patients with EPTB. Diagnosis of EPTB was reached using Microbiological Reference Standards (MRS) on samples from the disease site using WHO Recommended Diagnostics (WRD), [smear microscopy, liquid culture (MGIT-960)] and GX (molecular WRD, mWRD) and Comprehensive reference standards [CRS, clinical presentation, microbiological reference standards, radiology, histopathology]. GX-Ultra was performed on urine samples stored in -80oC deep freezer, retrospectively. Of 70 patients, 51 (72.9%) were classified as confirmed TB, 11 (15.7%) unconfirmed TB, and 8 (11.4%) unlikely TB. GX-Ultra in urine samples demonstrated sensitivity of 52.9% and specificity of 57.9% against MRS, and higher sensitivity of 56.5% and specificity of 100% against CRS. The sensitivity and specificity of GX-Ultra in urine was 53.6% and 75% for pus sample subset and 52.2% and 53.3% for fluid sample subset. Urine being non-invasive and easy to collect, detection of Mtb DNA using mWRD in urine samples is promising for diagnosis of EPTB.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. G. W. H. Organization;, “Global tuberculosis report,” (2021)

  2. Sharma SK, Mohan A (2004) “Extrapulmonary tuberculosis.,” Indian J. Med. Res, vol. 120, no. 4, pp. 316–53, Oct. [Online]. Available: http://www.ncbi.nlm.nih.gov/pubmed/15520485

  3. Lee JY (2015) Diagnosis and treatment of Extrapulmonary Tuberculosis. Tuberc Respir Dis (Seoul) 78(2):47. https://doi.org/10.4046/trd.2015.78.2.47

    Article  PubMed  Google Scholar 

  4. Lawn SD, Gupta-Wright A (2016) “Detection of lipoarabinomannan (LAM) in urine is indicative of disseminated TB with renal involvement in patients living with HIV and advanced immunodeficiency: evidence and implications,” Trans. R. Soc. Trop. Med. Hyg, vol. 110, no. 3, pp. 180–185, Mar. https://doi.org/10.1093/trstmh/trw008

  5. Labugger I et al (Jun. 2017) Detection of transrenal DNA for the diagnosis of pulmonary tuberculosis and treatment monitoring. ” Infect 45(3):269–276. https://doi.org/10.1007/s15010-016-0955-2

  6. Cannas A et al (2008) “Mycobacterium tuberculosis DNA detection in soluble fraction of urine from pulmonary tuberculosis patients.,” Int. J. Tuberc. Lung Dis, vol. 12, no. 2, pp. 146–51, [Online]. Available: http://www.ncbi.nlm.nih.gov/pubmed/18230246

  7. Wu X et al (2019) “Assessment of the Xpert MTB/RIF Ultra assay on rapid diagnosis of extrapulmonary tuberculosis,” Int. J. Infect. Dis, vol. 81, pp. 91–96, https://doi.org/10.1016/j.ijid.2019.01.050

  8. Sabi I et al (2022) Diagnosis of paediatric TB using Xpert ® MTB/RIF Ultra on fresh respiratory samples. Int J Tuberc Lung Dis 26(9):862–868. https://doi.org/10.5588/ijtld.22.0007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pang Y et al (Jul. 2017) GeneXpert MTB/RIF assay in the diagnosis of urinary tuberculosis from urine specimens. ” Sci Rep 7(1):6181. https://doi.org/10.1038/s41598-017-06517-0

  10. Graham SM et al (2015) “Clinical Case Definitions for Classification of Intrathoracic Tuberculosis in Children: An Update.,” Clin. Infect. Dis, vol. 61Suppl 3, pp. S179-87, https://doi.org/10.1093/cid/civ581

  11. Kent E, Kubica PT (1985) GP, Public health mycobacteriology: a guide for the Level III laboratory. Centers for Disease Control, Atlanta, GA

    Google Scholar 

  12. Forbes BA et al (Apr. 2018) Practical Guidance for Clinical Microbiology Laboratories: Mycobacteria. Clin Microbiol Rev 31(2). https://doi.org/10.1128/CMR.00038-17

  13. Mechal Y et al (Dec. 2019) Evaluation of GeneXpert MTB/RIF system performances in the diagnosis of extrapulmonary tuberculosis. BMC Infect Dis 19(1):1069. https://doi.org/10.1186/s12879-019-4687-7

  14. Singh UB et al (2016) Genotypic, phenotypic and clinical validation of GeneXpert in Extra-Pulmonary and Pulmonary Tuberculosis in India. ” PLoS One 11(2):e0149258. https://doi.org/10.1371/journal.pone.0149258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tuuminen T (2012) Urine as a Specimen to diagnose infections in Twenty-First Century: Focus on Analytical Accuracy. Front Immunol 3. https://doi.org/10.3389/fimmu.2012.00045

  16. Atherton RR et al (Oct. 2018) Detection of Mycobacterium tuberculosis in urine by Xpert MTB/RIF Ultra: a useful adjunctive diagnostic tool in HIV-associated tuberculosis. Int J Infect Dis 75:92–94. https://doi.org/10.1016/j.ijid.2018.07.007

  17. Yang X et al (2020) “Cell-free Mycobacterium tuberculosis DNA test in pleural effusion for tuberculous pleurisy: a diagnostic accuracy study,” Clin. Microbiol. Infect, vol. 26, no. 8, pp. 1089.e1-1089.e6, https://doi.org/10.1016/j.cmi.2019.11.026

  18. Park JH et al (2022) “Utility of plasma cell-free DNA detection using homobifunctional imidoesters using a microfluidic system for diagnosing active tuberculosis,” Infect. Dis. (Auckl), vol. 54, no. 1, pp. 46–52, https://doi.org/10.1080/23744235.2021.1963839

  19. Fernández-Carballo BL, Broger T, Wyss R, Banaei N, Denkinger CM (Apr. 2019) Toward the development of a circulating free DNA-Based in Vitro Diagnostic Test for Infectious Diseases: a review of evidence for tuberculosis. J Clin Microbiol 57(4). https://doi.org/10.1128/JCM.01234-18

  20. Click ES et al (Jan. 2018) Detection of apparent cell-free M. tuberculosis DNA from plasma. ” Sci Rep 8(1):645. https://doi.org/10.1038/s41598-017-17683-6

  21. Pan S-W et al (Nov. 2022) Circulating mitochondrial cell-free DNA dynamics in patients with mycobacterial pulmonary infections: potential for a novel biomarker of disease. Front Immunol 13. https://doi.org/10.3389/fimmu.2022.1040947

  22. Petrucci R et al (Jan. 2015) Use of Transrenal DNA for the diagnosis of Extrapulmonary Tuberculosis in Children: a case of Tubercular Otitis Media. J Clin Microbiol 53(1):336–338. https://doi.org/10.1128/JCM.02548-14

  23. Gopalaswamy R, Dusthackeer VNA, Kannayan S, Subbian S (May 2021) Extrapulmonary Tuberculosis—An update on the diagnosis, treatment and drug resistance. J Respir 1(2):141–164. https://doi.org/10.3390/jor1020015

  24. Hoel IM, Syre H, Skarstein I, Mustafa T (2020) Xpert MTB/RIF ultra for rapid diagnosis of extrapulmonary tuberculosis in a high-income low-tuberculosis prevalence setting. Sci Rep 10(1):1–7. https://doi.org/10.1038/s41598-020-70613-x

    Article  CAS  Google Scholar 

  25. Zhang M, Xue M, qing He J (2020) Diagnostic accuracy of the new Xpert MTB/RIF Ultra for tuberculosis disease: a preliminary systematic review and meta-analysis. Int Soc Infect Dis 90. https://doi.org/10.1016/j.ijid.2019.09.016

  26. Green C, Huggett JF, Talbot E, Mwaba P, Reither K, Zumla AI (Aug. 2009) Rapid diagnosis of tuberculosis through the detection of mycobacterial DNA in urine by nucleic acid amplification methods. ” Lancet Infect Dis 9(8):505–511. https://doi.org/10.1016/S1473-3099(09)70149-5

  27. “Circulating Tumor DNA Guiding Adjuvant Therapy in Colon Cancer,” N. Engl. J. Med., vol. 387, no. 8, pp. 759–760 (2022) https://doi.org/10.1056/NEJMc2209374

  28. Ssengooba W et al (2020) Accuracy of Xpert Ultra in diagnosis of pulmonary tuberculosis among children in Uganda: a Substudy from the SHINE Trial. J Clin Microbiol 58(9). https://doi.org/10.1128/JCM.00410-20

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Acknowledgements

The work reported was the analysis of patient diagnostic tests, carried out for patient care. We would like to acknowledge technical help from Ms. Megha (Junior Research Fellow).

Funding

This work was supported by the All India Institute of Medical Sciences, New Delhi, and FIND, the global alliance for diagnostics, Geneva.

Author information

Authors and Affiliations

  1. Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India

    Urvashi B. Singh, K. P. Angitha, Raunak Bir & Kiran Singh

  2. Department of Tuberculosis and Chest Diseases, Rajan Babu Institute for Pulmonary Medicine and Tuberculosis, New Delhi, India

    Anuj Bhatnagar

  3. Department of Pediatrics, National Institute of Tuberculosis and Respiratory Diseases, New Delhi, India

    Sangeeta Sharma

  4. The global alliance for diagnostics, FIND, Geneva, Switzerland

    Pamela Nabeta & Morten Ruhwald

  5. Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India

    Sushil K. Kabra & Rakesh Lodha

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  1. Urvashi B. Singh
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Contributions

UBS conceived the idea for the research and planned the work. UBS and AKP performed the literature search and wrote the article. UBS, RL, PN, and MR contributed to diagnostics and formal analysis. KS and RB contributed to laboratory management. UBS and RLcontributed to the study design, clinical discussion, and analysis. AB, SKK, SS, and RL contributed to clinical data and clinical care.

Corresponding author

Correspondence to Urvashi B. Singh.

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Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical Approval

Institutional ethical clearance from AIIMS, New Delhi, India, was obtained for the study (IEC-5/09.02.2017).

Consent to Participate

The procedures followed in the study were in accordance with the ethical standards of the Helsinki declaration (1964, amended most recently in 2008) of the World Medical Association. Written informed consent was obtained from all the patients or parents/guardians before inclusion in the study.

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Patients or parents/guardians signed informed consent regarding publishing their data.

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Electronic Supplementary Material

Below is the link to the electronic supplementary material.

284_2023_3503_MOESM1_ESM.pdf

Supplementary Table S1: Summary of results from EPTB samples used in the study.

Supplementary Material 2

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Singh, U.B., Angitha, K.P., Bhatnagar, A. et al. GeneXpert Ultra in Urine Samples for Diagnosis of Extra-Pulmonary Tuberculosis. Curr Microbiol 80, 361 (2023). https://doi.org/10.1007/s00284-023-03503-w

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