Diagnosis of smear-negative tuberculosis is greatly improved by Xpert MTB/RIF

Giulia Lombardi, Valentina Di Gregori, Nicolò Girometti, Marina Tadolini, Francesco Bisognin, Paola Dal Monte, Giulia Lombardi, Valentina Di Gregori, Nicolò Girometti, Marina Tadolini, Francesco Bisognin, Paola Dal Monte

Abstract

Background: Diagnosis of pulmonary (PTB) and extra-pulmonary tuberculosis (EPTB) in smear-negative patients can be difficult. We assessed retrospectively the performance of Xpert MTB/RIF system (Xpert, Cepheid) in diagnosing smear-negative tuberculosis (TB), which represents the most common form of TB in a low incidence setting.

Methods: Performance of Xpert was compared to acid-fast microscopic examination using Ziehl-Neelsen (ZN) stain in patients with culture-confirmed TB.

Results: 386 Mycobacterium tuberculosis (MTB) culture-positive samples were detected out of 5170 specimens tested with smear microscopy, Xpert and culture: 323 were both culture- and Xpert-positive, and 63 culture-positive only. Of these, 234 (60.6%) were smear-negative. In addition Xpert detected 40 probable TB cases, based on clinical findings, which were culture-negative. Compared to culture, Xpert showed an overall sensitivity of 83.7% and a specificity of 99.1%; sensitivity was higher for respiratory samples (86.5%) than for non-respiratory samples (76.8%). Xpert sensitivity for smear-negative culture-confirmed TB was 73.1% and was not influenced by TB localization. As sensitivity of microscopy alone was poor (39.4%), Xpert improved both diagnosis of pulmonary TB (Δ = 36.5%) and extra-pulmonary TB (Δ = 63.4%).

Conclusions: Xpert MTB/RIF is a sensitive method for rapid diagnosis of TB compared to the conventional ZN staining. Xpert can serve as a sensitive and time-saving diagnostic method for microbiological diagnosis of smear-negative TB in countries with a low TB prevalence.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Flow-chart of the study.
Fig 1. Flow-chart of the study.
MTB: Mycobacterium tuberculosis, NTM: Non-Tuberculous Mycobacteria.

References

    1. European Centre for Disease Prevention and Control/WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2015. Stockholm, Sweden: . Accessed October 21st 2016.
    1. World Health Organization. Antimicrobial resistance: global report on surveillance 2014. Geneva, Switzerland. . Accessed October 21st 2016.
    1. World Health Organization. Policy statement: automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB/RIF System. 2011. Geneva, Switzerland: . Accessed October 21st 2016
    1. Lawn SD, Nicol MP. Xpert® MTB/RIF assay: development, evaluation and implementation of a new rapid molecular diagnostic for tuberculosis and rifampicin resistance. Future Microbiol. 2011; 6(9):1067–1082. Review. Erratum in: Future Microbiol. 2012; 7(8):1024. 10.2217/fmb.11.84
    1. Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, et al. Rapid molecular detection of tuberculosis and rifampin resistance. New Engl J Med. 2010; 363(11):1005–1015. 10.1056/NEJMoa0907847
    1. Boehme CC, Nicol MP, Nabeta P, Michael JS, Gotuzzo E, Tahirli R, et al. Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study. Lancet. 2011; 377(9776):1495–1505. 10.1016/S0140-6736(11)60438-8
    1. Helb D, Jones M, Story E, Boehme C, Wallace E, Ho K, et al. Rapid detection of Mycobacterium tuberculosis and rifampin resistance by use of on-demand, near-patient technology. J Clin Microbiol. 2010; 48(1):229–237. 10.1128/JCM.01463-09
    1. Zeka AN, Tasbakan S, Cavusoglu C. Evaluation of the GeneXpert MTB/RIF assay for rapid diagnosis of tuberculosis and detection of rifampin resistance in pulmonary and extrapulmonary specimens. J Clin Microbiol. 2011;49(12):4138–4141. 10.1128/JCM.05434-11
    1. Marlowe EM, Novak-Weekley SM, Cumpio J, Sharp SE, Momeny MA, Babst A, et al. Evaluation of the Cepheid Xpert MTB/RIF assay for direct detection of Mycobacterium tuberculosis complex in respiratory specimens. J Clin Microbiol. 2011; 49(4):1621–1623. 10.1128/JCM.02214-10
    1. Sohn H, Aero AD, Menzies D, Behr M, Schwartzman K, Alvarez GG, et al. Xpert MTB/RIF testing in a low tuberculosis incidence, high-resource setting: limitations in accuracy and clinical impact. Clin Infect Dis. 2014; 58(7):970–976. 10.1093/cid/ciu022
    1. Opota O, Senn L, Prod'hom G, Mazza-Stalder J, Tissot F, Greub G, et al. Added value of molecular assay Xpert MTB/RIF compared to sputum smear microscopy to assess the risk of tuberculosis transmission in a low-prevalence country. Clin Microbiol Infect. 2016; 22(7):613–619. 10.1016/j.cmi.2016.04.010
    1. Borrini BM, Falaschi L, Finarelli AC, Marchi M, Mattivi A, Moro ML, et al. Epidemiologia della tubercolosi in Emilia-Romagna 2010–11. 2013. Bologna, Italy: . Accessed October 21st 2016.
    1. Lombardi G, Dal Monte P, Denicolò A, Tadolini M, Martelli G, Bacchi Reggiani ML, et al. Trend of microbiologically-confirmed tuberculosis in a low-incidence setting with high immigration rates. BMC Public Health. 2014; 14:340 10.1186/1471-2458-14-340
    1. Gazzetta Ufficiale n. 72 del 26 marzo 2012. Autorizzazione generale al trattamento dei dati personali effettuato per scopi di ricerca scientifica. . Accessed March 1st 2017.
    1. Weitzman I. Acid-fast stain In: Lynne S. Garcia editors. Clinical microbiology procedures handbook. 3th ed Washingoton, DC: ASM Press; 2010. 7.2.1–7.2.4.
    1. Clinical and Laboratory Standards Institute (CLSI). Laboratory detection and identification of mycobacteria; approved guideline, M48-A. 2008. Wayne, USA; . Accessed October 21st 2016
    1. Cepheid. Xpert MTB/RIF Package Insert. 2016. . Accessed October 21st 2016
    1. Kaur R, Kachroo K, Sharma JK, Vatturi SM, Dang A. Diagnostic accuracy of Xpert test in tuberculosis detection: a systematic review and meta-analysis. J Glob Infect Dis. 2016; 8(1):32–40. 10.4103/0974-777X.176143
    1. Meyer-Rath G, Schnippel K, Long L, MacLeod W, Sanne I, Stevens W, et al. The impact and cost of scaling up GeneXpert MTB/RIF in South Africa. PLoS One. 2012; 7(5):e36966 10.1371/journal.pone.0036966
    1. Tortoli E, Russo C, Piersimoni C, Mazzola E, Dal Monte P, Pascarella M, et al. Clinical validation of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis. Eur Respir J. 2012; 40(2):442–447. 10.1183/09031936.00176311
    1. Hillemann D, Rüsch-Gerdes S, Boehme C, Richter E. Rapid molecular detection of extrapulmonary tuberculosis by the automated GeneXpert MTB/RIF system. J Clin Microbiol. 2011; 49(4):1202–1205. 10.1128/JCM.02268-10
    1. Moure R, Muñoz L, Torres M, Santin M, Martín R, Alcaide F. Rapid detection of Mycobacterium tuberculosis complex and rifampin resistance in smear-negative clinical samples by use of an integrated real-time PCR method. J Clin Microbiol. 2011; 49(3):1137–1139. 10.1128/JCM.01831-10
    1. Walusimbi S, Bwanga F, De Costa A, Haile M, Joloba M, Hoffner S. Meta-analysis to compare the accuracy of GeneXpert, MODS and the WHO 2007 algorithm for diagnosis of smear-negative pulmonary tuberculosis. BMC Infectious Diseases. 2013; 13:507 10.1186/1471-2334-13-507
    1. Ramirez HL, García-Clemente MM, Alvarez-Álvarez C, Palacio-Gutierrez JJ, Pando-Sandoval A, Gagatek S, Arias-Guillén M, Quezada-Loaiza CA, Casan-Clará P. Impact of the Xpert (®) MTB/RIF molecular test on the late diagnosis of pulmonary tuberculosis. Int J Tuberc Lung Dis. 2014; 18(4):435–437. 10.5588/ijtld.13.0747
    1. Sharma SK, Kohli M, Yadav RN, Chaubey J, Bhasin D, Sreenivas V, et al. Evaluating the diagnostic accuracy of Xpert MTB/RIF assay in pulmonary tuberculosis. PLoS One. 2015; 10(10):e0141011 10.1371/journal.pone.0141011
    1. Li Q, Bao XD, Liu Y, Ou XC, Pang Y, Zhao YL. Comparison of Two Molecular Assays For Detecting Smear Negative Pulmonary Tuberculosis. Biomed Environ Sci. 2016;29(4):248–253. 10.3967/bes2016.032
    1. Reechaipichitkul W, Phetsuriyawong A, Chaimanee P, Ananta P. DIAGNOSTIC TEST OF SPUTUM GENEXPERT MTB/RIF FOR SMEAR NEGATIVE PULMONARY TUBERCULOSIS. Southeast Asian J Trop Med Public Health. 2016; 47(3):457–466.
    1. Maynard-Smith L, Larke N, Peters JA, Lawn SD. Diagnostic accuracy of the Xpert MTB/RIF assay for extrapulmonary and pulmonary tuberculosis when testing non-respiratory samples: a systematic review. BMC Infectious Diseases. 2014; 14: 709 10.1186/s12879-014-0709-7
    1. 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; 1: CD009593.
    1. Luetkemeyer AF, Firnhaber C, Kendall MA, Wu X, Mazurek GH, Benator DA, et al. Evaluation of Xpert MTB/RIF versus AFB smear and culture to identify pulmonary tuberculosis in patients with suspected tuberculosis from low and higher prevalence settings. Clin Infect Dis. 2016; 62(9):1081–1088. 10.1093/cid/ciw035
    1. Muñoz L, Moure R, Porta N, Gonzalez L, Guerra R, Alcaide F, et al. GeneXpert® for smear-negative pulmonary tuberculosis: does it play a role in low-burden countries? Diagn Microbiol Infect Dis. 2013; 75(3):325–326. 10.1016/j.diagmicrobio.2012.11.011
    1. Wei G, Mu J, Wang G, Huo F, Dong L, Li Y, et al. The reliability analysis of Xpert-positive result for smear-negative and culture-negative specimen collected from bone and joint tuberculosis suspects. J Thorac Dis. 2016; 8(6):1205–1209. 10.21037/jtd.2016.04.19
    1. Blakemore R, Story E, Helb D, Kop J, Banada P, Owens MR, et al. Evaluation of the analytical performance of the Xpert MTB/RIF assay. J Clin Microbiol. 2010; 48(7):2495–2501. 10.1128/JCM.00128-10
    1. Tadesse M, Aragaw D, Rigouts L, Abebe G. Increased detection of smear-negative pulmonary tuberculosis by GeneXpert MTB/RIF® assay after bleach concentration. Int J Mycobacteriol. 2016; 5(2):211–218. 10.1016/j.ijmyco.2016.03.005
    1. Le Palud P, Cattoir V, Malbruny B, Magnier R, Campbell K, Oulkhouir Y, et al. Retrospective observational study of diagnostic accuracy of the Xpert® MTB/RIF assay on fiberoptic bronchoscopy sampling for early diagnosis of smear-negative or sputum-scarce patients with suspected tuberculosis. BMC Pulm Med. 2014; 14:137 10.1186/1471-2466-14-137

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever