A pre-clinical validation plan to evaluate analytical sensitivities of molecular diagnostics such as BD MAX MDR-TB, Xpert MTB/Rif Ultra and FluoroType MTB


Autoři: Markus Beutler aff001;  Sara Plesnik aff001;  Marina Mihalic aff001;  Laura Olbrich aff002;  Norbert Heinrich aff002;  Samuel Schumacher aff004;  Michael Lindner aff005;  Ina Koch aff005;  Wolfgang Grasse aff006;  Christoph Metzger-Boddien aff006;  Sabine Hofmann-Thiel aff001;  Harald Hoffmann aff001
Působiště autorů: Institute of Microbiology and Laboratory Medicine, Department IML Red GmbH, WHO-Supranational Reference Laboratory of Tuberculosis, Munich-Gauting, Germany aff001;  Division of Infectious Diseases and Tropical Medicine, LMU University Hospital, Munich, Germany aff002;  German Centre of Research on Infectious Diseases (DZIF), Partner Site Munich, Germany aff003;  Foundation for Innovative New Diagnostics, Geneva, Switzerland aff004;  Asklepios Fachkliniken München-Gauting, Munich, Germany aff005;  gerbion GmbH & Co. KG, Kornwestheim, Germany aff006;  SYNLAB Gauting, SYNLAB Human Genetics Munich, Munich-Gauting, Germany aff007
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227215

Souhrn

Rapid diagnosis of tuberculosis (TB) and antibiotic resistances are imperative to initiate effective treatment and to stop transmission of the disease. A new generation of more sensitive, automated molecular TB diagnostic tests has been recently launched giving microbiologists more choice between several assays with the potential to detect resistance markers for rifampicin and isoniazid. In this study, we determined analytical sensitivities as 95% limits of detection (LoD95) for Xpert MTB/Rif Ultra (XP-Ultra) and BD-MAX MDR-TB (BD-MAX) as two representatives of the new test generation, in comparison to the conventional FluoroType MTB (FT-MTB). Test matrices used were physiological saline solution, human and a mucin-based artificial sputum (MUCAS) each spiked with Mycobacterium tuberculosis in declining culture- and qPCR-controlled concentrations. With BD-MAX, XP-Ultra, and FT-MTB, we measured LoD95TB values of 2.1 cfu/ml (CI95%: 0.9–23.3), 3.1 cfu/ml (CI95%: 1.2–88.9), and 52.1 cfu/ml (CI95%: 16.7–664.4) in human sputum; of 6.3 cfu/ml (CI95%: 2.9–31.8), 1.5 cfu/ml (CI95%: 0.7–5.0), and 30.4 cfu/ml (CI95%: 17.4–60.7) in MUCAS; and of 2.3 cfu/ml (CI95%: 1.1–12.0), 11.5 cfu/ml (CI95%: 5.6–47.3), and 129.1 cfu/ml (CI95%: 82.8–273.8) in saline solution, respectively. LoD95 of resistance markers were 9 to 48 times higher compared to LoD95TB. BD-MAX and XP-Ultra have an equal and significantly increased analytical sensitivity compared to conventional tests. MUCAS resembled human sputum, while both yielded significantly different results than normal saline. MUCAS proved to be suitable for quality control of PCR assays for TB diagnostics.

Klíčová slova:

Antibiotic resistance – Multi-drug-resistant tuberculosis – Mycobacterium tuberculosis – Polymerase chain reaction – Sputum – Tuberculosis – Tuberculosis diagnosis and management – Saline solutions


Zdroje

1. WHO. Global tuberculosis report 2018. In: WHO [Internet]. 2018 [cited 22 Feb 2019]. Available: http://www.who.int/tb/publications/global_report/en/

2. Franco-Sotomayor G, Garzon-Chavez D, Leon-Benitez M, de Waard JH, Garcia-Bereguiain MA. A First Insight into the katG and rpoB Gene Mutations of Multidrug-Resistant Mycobacterium tuberculosis Strains from Ecuador. Microb Drug Resist Larchmt N. 2018. doi: 10.1089/mdr.2018.0203 30513056

3. Orenstein EW, Basu S, Shah NS, Andrews JR, Friedland GH, Moll AP, et al. Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis. Lancet Infect Dis. 2009;9: 153–161. doi: 10.1016/S1473-3099(09)70041-6 19246019

4. Tang S, Tan S, Yao L, Li F, Li L, Guo X, et al. Risk Factors for Poor Treatment Outcomes in Patients with MDR-TB and XDR-TB in China: Retrospective Multi-Center Investigation. PLOS ONE. 2013;8: e82943. doi: 10.1371/journal.pone.0082943 24349402

5. Shah NS, Wright A, Bai G-H, Barrera L, Boulahbal F, Martín-Casabona N, et al. Worldwide Emergence of Extensively Drug-resistant Tuberculosis. Emerg Infect Dis. 2007;13: 380–387. doi: 10.3201/eid1303.061400 17552090

6. Nathanson E, Nunn P, Uplekar M, Floyd K, Jaramillo E, Lönnroth K, et al. MDR Tuberculosis—Critical Steps for Prevention and Control. N Engl J Med. 2010;363: 1050–1058. doi: 10.1056/NEJMra0908076 20825317

7. Nema V. Tuberculosis diagnostics: Challenges and opportunities. Lung India Off Organ Indian Chest Soc. 2012;29: 259–266. doi: 10.4103/0970-2113.99112 22919166

8. Antonenka U, Hofmann-Thiel S, Turaev L, Esenalieva A, Abdulloeva M, Sahalchyk E, et al. Comparison of Xpert MTB/RIF with ProbeTec ET DTB and COBAS TaqMan MTB for direct detection of M. tuberculosis complex in respiratory specimens. BMC Infect Dis. 2013;13: 280. doi: 10.1186/1471-2334-13-280 23786563

9. Hofmann-Thiel S, Hoffmann H. Evaluation of Fluorotype MTB for detection of Mycobacterium tuberculosis complex DNA in clinical specimens from a low-incidence country. BMC Infect Dis. 2014;14: 59. doi: 10.1186/1471-2334-14-59 24498967

10. Steingart KR, Schiller I, Horne DJ, Pai M, Boehme CC, Dendukuri N. Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev. 2014 [cited 16 Jan 2019]. doi: 10.1002/14651858.CD009593.pub3 24448973

11. Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, et al. Rapid Molecular Detection of Tuberculosis and Rifampin Resistance. N Engl J Med. 2010;363: 1005–1015. doi: 10.1056/NEJMoa0907847 20825313

12. Albert H, Nathavitharana RR, Isaacs C, Pai M, Denkinger CM, Boehme CC. Development, roll-out and impact of Xpert MTB/RIF for tuberculosis: what lessons have we learnt and how can we do better? Eur Respir J. 2016;48: 516–525. doi: 10.1183/13993003.00543-2016 27418550

13. Calligaro GL, Zijenah LS, Peter JG, Theron G, Buser V, McNerney R, et al. Effect of new tuberculosis diagnostic technologies on community-based intensified case finding: a multicentre randomised controlled trial. Lancet Infect Dis. 2017;17: 441–450. doi: 10.1016/S1473-3099(16)30384-X 28063795

14. Chakravorty S, Simmons AM, Rowneki M, Parmar H, Cao Y, Ryan J, et al. The New Xpert MTB/RIF Ultra: Improving Detection of Mycobacterium tuberculosis and Resistance to Rifampin in an Assay Suitable for Point-of-Care Testing. Nacy CA, editor. mBio. 2017;8. doi: 10.1128/mBio.00812-17 28851844

15. Zimmermann S, Dalpke A, Murray P, Paradis S, Cooper C. Pre-validation of the BD MAX MDR-TB* assay for the rapid detection of MTBc DNA and mutations associated with rifampin and isoniazid resistance Introduction Results. In: ResearchGate [Internet]. 4 Apr 2018 [cited 22 Feb 2019]. Available: https://www.researchgate.net/publication/324804012_Pre-validation_of_the_BD_MAX_MDR-TB_assay_for_the_rapid_detection_of_MTBc_DNA_and_mutations_associated_with_rifampin_and_isoniazid_resistance_Introduction_Results

16. Hofmann-Thiel S, Molodtsov N, Antonenka U, Hoffmann H. Evaluation of the Abbott RealTi m e MTB and RealTi m e MTB INH/RIF Assays for Direct Detection of Mycobacterium tuberculosis Complex and Resistance Markers in Respiratory and Extrapulmonary Specimens. Land GA, editor. J Clin Microbiol. 2016;54: 3022–3027. doi: 10.1128/JCM.01144-16 27733630

17. Hofmann-Thiel S, Molodtsov N, Duffner C, Kadyrov A, Kalmambetova G, Kabirov O, et al. Capacity of Abbott RealTime MTB RIF/INH to detect rifampicin- and isoniazid-resistant tuberculosis. 1 Apr 2019 [cited 20 May 2019]. doi: 10.5588/ijtld.18.0615 31064625

18. Diraviam Dinesh S. Artificial Sputum Medium. Protoc Exch. 2010 [cited 22 Feb 2019]. doi: 10.1038/protex.2010.212

19. Yamada H, Mitarai S, Wahyunitisari MR, Mertaniasih NM, Sugamoto T, Chikamatsu K, et al. Improved Polyacrylamide-Based Artificial Sputum with Formalin-Fixed Tubercle Bacilli for Training of Tuberculosis Microscopists. J Clin Microbiol. 2011;49: 3604–3609. doi: 10.1128/JCM.00370-11 21813720

20. Rogers JV, Choi YW. Preliminary Evaluation of Mycobacterium tuberculosis Detection in Culture and Artificial Sputum Using a BioNanoPore Membrane and Real-time PCR. J Microb Biochem Technol. 2012;4: 147–151.

21. Kent PT, Kubica GP. Public Health Mycobacteriology: A Guide for the Level III Laboratory. | National Technical Reports Library—NTIS. 1985 [cited 8 May 2019]. Available: https://ntrl.ntis.gov/NTRL/dashboard/searchResults/titleDetail/PB86216546.xhtml

22. Peñuelas-Urquides K, Villarreal-Treviño L, Silva-Ramírez B, Rivadeneyra-Espinoza L, Said-Fernández S, León MB de. Measuring of Mycobacterium tuberculosis growth: a correlation of the optical measurements with colony forming units. Braz J Microbiol. 2013;44: 287–290. doi: 10.1590/S1517-83822013000100042 24159318

23. Burdz TVN, Wolfe J, Kabani A. Evaluation of sputum decontamination methods for Mycobacterium tuberculosis using viable colony counts and flow cytometry. Diagn Microbiol Infect Dis. 2003;47: 503–509. doi: 10.1016/s0732-8893(03)00138-x 14596969

24. Zheng H, Lu L, Wang B, Pu S, Zhang X, Zhu G, et al. Genetic Basis of Virulence Attenuation Revealed by Comparative Genomic Analysis of Mycobacterium tuberculosis Strain H37Ra versus H37Rv. PLOS ONE. 2008;3: e2375. doi: 10.1371/journal.pone.0002375 18584054

25. Luo Y, Roux B. Simulation of Osmotic Pressure in Concentrated Aqueous Salt Solutions. J Phys Chem Lett. 2010;1: 183–189. doi: 10.1021/jz900079w

26. WHO. WHO meeting report of a technical expert consultation: non-inferiority analysis of Xpert MTB/RIF Ultra compared to Xpert MTB/RIF. World Health Organization; 2017.

27. Mokaddas EM, Ahmad S, Eldeen HS. GeneXpert MTB/RIF Is Superior to BBD Max MDR-TB for Diagnosis of Tuberculosis (TB) in a Country with Low Incidence of Multidrug-Resistant TB (MDR-TB). J Clin Microbiol. 2019;57: e00537–19. doi: 10.1128/JCM.00537-19 30971464

28. Shah M, Paradis S, Betz J, Beylis N, Bharadwaj R, Caceres T, et al. Multicenter Study of the Accuracy of the BD MAXTM MDR-TB Assay for Detection of Mycobacterium tuberculosis Complex and Mutations Associated with Resistance to Rifampin and Isoniazid. Clin Infect Dis Off Publ Infect Dis Soc Am. 2019. doi: 10.1093/cid/ciz932 31560049

29. Andrews RH, Radhakrishna S. A Comparison of Two Methods of Sputum Collection in the Diagnosis of Pulmonary Tuberculosis. Tubercle. 1959;40: 155–62. Available: https://www.cabdirect.org/cabdirect/abstract/19602700098 doi: 10.1016/s0041-3879(59)80034-9 13793613

30. Boat TF, Cheng PW, Iyer RN, Carlson DM, Polony I. Human respiratory tract secretions: Mucous glycoproteins of nonpurulent tracheobronchial secretions, and sputum of patients with bronchitis and cystic fibrosis. Arch Biochem Biophys. 1976;177: 95–104. doi: 10.1016/0003-9861(76)90419-7 999298

31. Stockley RA, Bayley D, Hill SL, Hill AT, Crooks S, Campbell EJ. Assessment of airway neutrophils by sputum colour: correlation with airways inflammation. Thorax. 2001;56: 366–372. doi: 10.1136/thorax.56.5.366 11312405

32. Zhao J, Li J, Schloss PD, Kalikin LM, Raymond TA, Petrosino JF, et al. Effect of Sample Storage Conditions on Culture-Independent Bacterial Community Measures in Cystic Fibrosis Sputum Specimens. J Clin Microbiol. 2011;49: 3717–3718. doi: 10.1128/JCM.01189-11 21865433

33. Miotto P, Tessema B, Tagliani E, Chindelevitch L, Starks AM, Emerson C, et al. A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis. Eur Respir J. 2017;50: 1701354. doi: 10.1183/13993003.01354-2017 29284687


Článek vyšel v časopise

PLOS One


2020 Číslo 1