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Diagnostic value of nine nucleic acid amplification test systems for Mycobacterium tuberculosis complex

Year 2015, Volume: 5 Issue: 3, 103 - 109, 06.02.2016

Gülnur Tarhan Salih Cesur , Hülya Şimşek Ismail Ceyhan Yusuf Ozay Melike Atasever

https://doi.org/10.5799/ahinjs.02.2015.03.0186
Cited By: 1

Abstract

Objective: In this study, nine commercial Nucleic Acid Amplification Test Systems (NAATs) were evaluated for diagnostic performance of Mycobacterium tuberculosis complex (MTBC) from smear positive sputum species (SPss) and smear negative sputum specimens (SNss). Methods: Sixty SPss and 55 SNss were examined microscopically by Ehrlich Ziehl Neelsen (EZN) staining method, and also inoculated on Löwenstein Jensen (LJ) medium for culture. The sensitivity and specificity of nine NAATs were calculated according to LJ culture method accepted as gold standard. Results: When LJ culture results were taken as gold standard; the sensitivity rates of method COBAS Amplicor MTB (Method A), GenProbe MTD (Method B), Cobas TaqMan MTB PCR (Method C), iCycler iQ RT PCR (Method D), TaqMan PCR AB 5700 (Method E), TaqMan PCR AB7700 (Method F), LightCycler® 480 RT PCR (Method G), Rotor Gene RT PCR (Method H) and the AdvanSure TB/NTM RT PCR (Method I) for SPss were 98.3 %, 93.3 %, 96.7 %, 100 %, 93.3 %, 100 %, 100 %, 100 % and 100 %, respectively. The sensitivity was 53.84% for the methods A, B, D, E, G and I; 38.46% for the method C and H; 61.5% for the method F for the method I in SNss. There were no statistical significant differences between the nine NAATs (p≥0.05). The specificity was 100% for all nine NAATs in SNss. The positivity rates of methods were 53.8% for methods A, B, D, E, G, I; 38.5% for methods C and H, and 61.5% for method F in SNss. These rates were 100% for D, F, G, H and I; 98.3% for method A; 96.7% for method C; 93,3% for methods B and E in SPss. Statistical analysis showed that there was no statistically significant differences among the nine NAATs (p≥0.05).

Conclusion: It is concluded that the nine NAATs might be useful for detecting MTBC from SPss, but not effective for SNss. J Microbiol Infect Dis 2015;5(3): 103-109

Key words: Tuberculosis, polymerase chain reaction, nucleic acid amplification test, smear positive, smear negative, sputum

Keywords

Tuberculosis polymerase chain reaction nucleic acid amplification test smear positive smear negative sputum

References

  • T.C.Sağlık Bakanlığı Verem Savaş Daire Başkanlığı, Türkiye’de
  • Verem Savaşı 2011 Raporu 5-9.
  • International Standards for Tuberculosis Care. 2013; Available
  • from: http://www.who.int/tb/publications/2006/istc_report.pdf, accessed on March 6.
  • World Health Organization Global tuberculosis control:
  • surveillance,planning, financing 2008;1-2.
  • Gebre N. Improved microscopical diagnosis of PTB in developing
  • countries. Trans Royal Soc Trap Med Hyg 1995;89:191-193.
  • World Health Organization.Tuberculosis Diagnostic Workshop:
  • Product Development guidelines 1997;21-24.
  • World Health Organization. Laboratory services in tuberculosis
  • control part III culture. Global Tuberculosis Programme 1998; 47-52.
  • Lambi EA. Medium selection and incubation for the isolation of
  • Mycobacteria, In: Isenberg HD, editor. Clinical microbiology
  • procedures handbook. Vol. 1. Washington, D.C. American Society for Microbiology. 1993; 3.6.1-3.6.8.
  • Metchock BG, Nolte FS, Wallace Jr RJ. Mycobacterium. In:Murray PR, Baron EJ, Pfaller MA et al, editors. Manual of clinical microbiology 7th ed. Washington, D.C. American Society for Microbiology 1999;399-437.
  • Diagnostic standards and classification of tuberculosis (1990)
  • American Thoracic Society Am Rev Respir Dis 1990;142:725–735.
  • Waard JH, Robledo J.Conventional diagnostic methods. In:
  • Palomino JC, Leão SC, Ritacco V (editors). Tuberculosis (Available from: www.TuberculosisTextbook.com). 2007;12:401-424.
  • Bogard M, Vincelette J, Antinozzi R, et al. Multicenter study of a commercial, automated polymerase chain reaction system for the rapid detection of Mycobacterium tuberculosis in respiratory specimens in routine clinical practice. Eur J Clin Microbiol Infect Dis 2001; 20:724–731.
  • Greco S, Girardi E, Navarra A, Saltini C. Current evidence on
  • diagnostic accuracy of commercially based nucleic acid amplification
  • tests for the diagnosis of pulmonary tuberculosis.Thorax 2006; 61:783–790.
  • Balasingham SV, Davidsen TI, Szpinda SA, Tonjum T. Molecular
  • diagnostics in tuberculosis: basis and implications for therapy. Mol Diagn Ther 2009; 13:137–151.
  • Laraque F, Griggs A, Slopen M, Munsiff SS. Performance of nucleic acid amplification tests for diagnosis of tuberculosis
  • in a large urban setting. Clin Infect Dis 2009; 49:46–54.
  • Ling DI, Flores LL, Riley LW, Pai M. Commercial nucleic-acid
  • amplification tests for diagnosis of pulmonary tuberculosis in
  • respiratory specimens: meta-analysis and meta-regressionPLoS One 2008; 3:e1536.
  • Noordhoek GT, Mulder S, Wallace P, van Loon AM. Multicentre
  • quality control study for detection of Mycobacterium tuberculosis
  • in clinical samples by nucleic amplification methods.Clin Microbiol Infect 2004;10:295-301.
  • World Health Organization.Tuberculosis Diagnostic Technology
  • Landscape 2012;19-23.
  • Centers for Disease Control and Prevention (CDC). Update:
  • nucleic acid amplification tests for tuberculosis. MMWR Morb Mortal Wkly Rep 2000; 49:593–594.
  • World Health Organization. New technologies for tuberculosis
  • control: a framework for their adoption, introduction and implementation; 2007.
  • Centers for Disease Control and Prevention (CDC). Updated
  • guidelines for the use of nucleic acid amplification tests in the
  • diagnosis of tuberculosis. MMWR 2009;58:7-10.
  • .Reischl U, Lehn N, Wolf H, Naumann L. Clinical evaluation
  • of the automated COBAS AMPLICOR MTB assay for testing
  • respiratory and non-respiratory specimens. J Clin Microbiol1998;
  • :2853-60.
  • Chang HE, Heo SR, Yoo KC, et al. Detection of Mycobacterium
  • tuberculosis complex using real-time polymerase chain reaction. Korean J Lab Med 2008; 28:103–108.
  • Ortu S, Molicotti P, Sechi LA, et al. Rapid detection and identification of Mycobacterium tuberculosis by Real Time PCR
  • and Bactec 960 MIGT. New Microbiol 2006;29: 75-80.
  • Jung CL, Kim MK, Seo DC, Lee MA. Clinical usefulness of
  • real-time PCR and amplicor MTB PCR assays for diagnosis of tuberculosis. Korean J Clin Microbiol. 2008; 11:29–33.
  • Piersimoni C, Scarparo C. Relevance of commercial amplification
  • methods for direct detection of Mycobacterium tuberculosis complex in clinical samples. J Clin Microbiol 2003;41:5355-5365.
  • Dinnes, J., et al.A systematic review of rapid diagnostic tests
  • for the detection of tuberculosis infection. Health Technol Assess
  • ;11:119–196.
  • Flores LL, Pai M, M. Colford J, et al. In-house nucleic acid amplification tests for the detection of Mycobacterium tuberculosisin
  • sputum specimens: meta-analysis and metaregression.BMC Microbiol 2005; 5:55.
  • Tan WY, Stratton CW. Diagnosis of Mycobacterium tuberculosis.
  • Advanced techniques in diagnostic microbiology, 2nd Edition. Springer Newyork Heidelberg Dordrecht, London 2006;567.
  • Kubica GPW, Dye E, Cohn ML, Middlebrook G. Sputum digestion
  • and decontamination with N-acetyl-Lcysteine- sodium hydroxide for culture of mycobacteria. Am Rev Respir Dis 1963; 87:775-779.
  • Waard JH, Robledo. Conventional diagnostic methods. In:
  • Palomino JC, Leão SC, Ritacco V (editors). Tuberculosis (Available from: www.TuberculosisTextbook.com). 2007;12:401-424.
  • Tuberculosis Division, International Union Against Tuberculosis
  • and Lung Disease. Tuberculosis bacteriology- priorities and indications in high prevalence countries: position of the technical staff of the Tuberculosis Division of the International Union Against. Int J Tuberc Lung Dis 2005; 9:355-361.
  • Telenti A, Marchesi F, Balz M, et al. Rapid identification of mycobacteria to the species level by polymerase chain reaction
  • and restriction enzyme analysis. J Clin Microbiol 1993;31:175–178.
  • Vincent V, Brown-Elliott BA, Jost KC, Wallace RJ. Mycobacterium:
  • phenotypic and genotypic identification, In Murray P. R., Baron E. J., Baron E. J., Pfaller M. A., Yolken R. H., editors.(ed.), Manual of clinical microbiology, 8th ed. American Society for Microbiology, Washington, DC.2003; p. 560–584.
  • Amplied MTD Test (amplified Mycobacterium tuberculosis
  • direct test for in vitro diagnostic use) [package insert] San Diego, CA: Gen-Probe 2001.
  • MagNA Pure LC Total Nucleic Acid Isolation Kit (Available
  • from:www.http://www.roche-applied-cience.com/shop/products/magna-pure-lc-total-nucleic-acid-isolation-kit)
  • Roche Molecular Systems, Inc, COBAS TaqMan MTB test
  • (2007) Roche Molecular Systems, Inc., Branchburg, NJ.
  • Biorad iCycler iQ™. Real-Time PCR Detection System. Instruction
  • Manual. Catalog Number: 170-8740.
  • Applied Biosystems, TaqMan® Universal PCR Master Mix,
  • Instruction Manual. Available from: www.appliedbiosystems.com
  • The LightCycler® 480 Real-Time PCR System Guide (2008)
  • Roche Applied Science, 68298 Mannheim, Germany, Roche
  • Diagnostics.
  • Rotor-Gene® Q and artus® PCR Kits -Pure Pathogen Detection
  • (2010) Available from: www.qiagen.com
  • AdvanSure TB/NTM real-time PCR kit procedures, LG Life
  • Sciences, Seul, Korea
  • Gardner MJ, Altman DG (ed.) Statistics with confidence. BMJ
  • Publishing Group, London, United Kingdom. 1989.
  • Gamboa F, Manterola JM, Lonca J, et al. Comparative evaluation
  • of two commercial assays for direct detection of Mycobacterium
  • tuberculosis in respiratory specimens. Eur J Clin Microbiol Infect Dis 1998; 17:151–156.
  • Kim YJ, Park MY, Kim SY, et al. Evaluation of the performances
  • of advanSure TB/NTM real time PCR Kit for detection of mycobacteria in respiratory specimens. Korean J Lab Med 2008; 28:34–38.
  • Yang YC, Lu PL, Huang SC, et al. Evaluation of the Cobas Taq Man MTB test for direct detection of Mycobacterium tuberculosis
  • complex in respiratory specimens. J Clin Microbiol 2011; 49(3):797-801. doi: 10.1128/JCM.01839-10.
  • Kim JH, Kim YJ, Ki CS, et al. Evaluation of COBAS TaqMan MTB PCR for detection of Mycobacterium tuberculosis. J Clin Microbiol 2011; 49:173–176.

-

Year 2015, Volume: 5 Issue: 3, 103 - 109, 06.02.2016

Gülnur Tarhan Salih Cesur , Hülya Şimşek Ismail Ceyhan Yusuf Ozay Melike Atasever

https://doi.org/10.5799/ahinjs.02.2015.03.0186
Cited By: 1

Abstract

Amaç: Bu çalışmada, yayma pozitif balgam örneklerinde ve yayma negatif balgam örneklerinde Mycobacterium tuberculosis kompleks (MTBK)’nin hızlı tanısında dokuz ticari Nükleik Asit Amplifikasyon Test sistemi (NAAT)’nin tanı performansı değerlendirildi. Yöntemler: Çalışma sırasında kullanılan 60 yayma pozitif ve 55 yayma negatif balgam örneği mikroskopik olarak Erlich Zielh Neelsen (EZN) boyama yöntemi ve Löwenstein Jensen (LJ) besiyerinde kültür ile değerlendirildi. Löwenstein-Jensen kültür yöntemi altın standart olarak kabul edilerek dokuz NAAT yönteminin duyarlılık ve özgüllükleri hesaplandı.Bulgular: Löwenstein Jensen kültür sonuçları altın standart olarak alındığında; Yayma pozitif örneklerde (COBAS Amplicor MTB (Metot A), GenProbe MTD (Metot B), Cobas TaqMan MTB PCR (Metot C), iCycler iQ RT-PCR (Metot D), TaqMan PCR AB 5700 (Metot E), TaqMan PCR AB7700 (Metot F), LightCycler® 480 RT PCR (Metot G), Rotor Gene RT PCR (Metot H) ve AdvanSure TB/NTM RT PCR (Metot I) yöntemlerinin duyarlılık oranı sırası ile % 98,3, % 93,3, % 96,7, % 100, % 93,3, % 100, % 100, % 100 ve % 100 olarak bulundu. Bu oran yayma negatif örneklerde A, B, D, E, G ve I yöntemleri için % 53,8; C ve H yöntemi için % 38,5; F yöntemi için % 61,5 olarak bulundu. Dokuz NAAT metodu arasında istatistiksel olarak anlamlı fark bulunmadı. (p≥0.05). Yayma negatif balgam örneklerinde özgüllük bütün NAAT yöntemleri için % 100 olarak saptandı. Pozitif saptama oranı yayma negatif örneklerde A, B, D, E, G ve I yöntemleri için % 53,8, C ve H yöntemleri için % 38,5 ve F yöntemi için % 61,5 olarak bulundu. Bu oran yayma pozitif balgam örneklerinde D, F, G, H ve I yöntemleri için % 100; A yöntemi için % 98,3, C yöntemi için % 96,7, B ve E yöntemleri için % 93,3 olarak saptandı. Dokuz NAAT yöntemi arasında istatistiksel olarak anlamlı fark bulunmadı (p≥0.05). Sonuç: Dokuz NAAT yönteminin yayma pozitif örneklerde MTBK tanısında yararlı olabileceği, ancak yayma negatif örneklerde etkin olmadığı sonucuna varıldı

Keywords

Tüberküloz polimeraz zincir reaksiyonu nükleik asit amplifikasyon test yayma pozitif yayma negatif

References

  • T.C.Sağlık Bakanlığı Verem Savaş Daire Başkanlığı, Türkiye’de
  • Verem Savaşı 2011 Raporu 5-9.
  • International Standards for Tuberculosis Care. 2013; Available
  • from: http://www.who.int/tb/publications/2006/istc_report.pdf, accessed on March 6.
  • World Health Organization Global tuberculosis control:
  • surveillance,planning, financing 2008;1-2.
  • Gebre N. Improved microscopical diagnosis of PTB in developing
  • countries. Trans Royal Soc Trap Med Hyg 1995;89:191-193.
  • World Health Organization.Tuberculosis Diagnostic Workshop:
  • Product Development guidelines 1997;21-24.
  • World Health Organization. Laboratory services in tuberculosis
  • control part III culture. Global Tuberculosis Programme 1998; 47-52.
  • Lambi EA. Medium selection and incubation for the isolation of
  • Mycobacteria, In: Isenberg HD, editor. Clinical microbiology
  • procedures handbook. Vol. 1. Washington, D.C. American Society for Microbiology. 1993; 3.6.1-3.6.8.
  • Metchock BG, Nolte FS, Wallace Jr RJ. Mycobacterium. In:Murray PR, Baron EJ, Pfaller MA et al, editors. Manual of clinical microbiology 7th ed. Washington, D.C. American Society for Microbiology 1999;399-437.
  • Diagnostic standards and classification of tuberculosis (1990)
  • American Thoracic Society Am Rev Respir Dis 1990;142:725–735.
  • Waard JH, Robledo J.Conventional diagnostic methods. In:
  • Palomino JC, Leão SC, Ritacco V (editors). Tuberculosis (Available from: www.TuberculosisTextbook.com). 2007;12:401-424.
  • Bogard M, Vincelette J, Antinozzi R, et al. Multicenter study of a commercial, automated polymerase chain reaction system for the rapid detection of Mycobacterium tuberculosis in respiratory specimens in routine clinical practice. Eur J Clin Microbiol Infect Dis 2001; 20:724–731.
  • Greco S, Girardi E, Navarra A, Saltini C. Current evidence on
  • diagnostic accuracy of commercially based nucleic acid amplification
  • tests for the diagnosis of pulmonary tuberculosis.Thorax 2006; 61:783–790.
  • Balasingham SV, Davidsen TI, Szpinda SA, Tonjum T. Molecular
  • diagnostics in tuberculosis: basis and implications for therapy. Mol Diagn Ther 2009; 13:137–151.
  • Laraque F, Griggs A, Slopen M, Munsiff SS. Performance of nucleic acid amplification tests for diagnosis of tuberculosis
  • in a large urban setting. Clin Infect Dis 2009; 49:46–54.
  • Ling DI, Flores LL, Riley LW, Pai M. Commercial nucleic-acid
  • amplification tests for diagnosis of pulmonary tuberculosis in
  • respiratory specimens: meta-analysis and meta-regressionPLoS One 2008; 3:e1536.
  • Noordhoek GT, Mulder S, Wallace P, van Loon AM. Multicentre
  • quality control study for detection of Mycobacterium tuberculosis
  • in clinical samples by nucleic amplification methods.Clin Microbiol Infect 2004;10:295-301.
  • World Health Organization.Tuberculosis Diagnostic Technology
  • Landscape 2012;19-23.
  • Centers for Disease Control and Prevention (CDC). Update:
  • nucleic acid amplification tests for tuberculosis. MMWR Morb Mortal Wkly Rep 2000; 49:593–594.
  • World Health Organization. New technologies for tuberculosis
  • control: a framework for their adoption, introduction and implementation; 2007.
  • Centers for Disease Control and Prevention (CDC). Updated
  • guidelines for the use of nucleic acid amplification tests in the
  • diagnosis of tuberculosis. MMWR 2009;58:7-10.
  • .Reischl U, Lehn N, Wolf H, Naumann L. Clinical evaluation
  • of the automated COBAS AMPLICOR MTB assay for testing
  • respiratory and non-respiratory specimens. J Clin Microbiol1998;
  • :2853-60.
  • Chang HE, Heo SR, Yoo KC, et al. Detection of Mycobacterium
  • tuberculosis complex using real-time polymerase chain reaction. Korean J Lab Med 2008; 28:103–108.
  • Ortu S, Molicotti P, Sechi LA, et al. Rapid detection and identification of Mycobacterium tuberculosis by Real Time PCR
  • and Bactec 960 MIGT. New Microbiol 2006;29: 75-80.
  • Jung CL, Kim MK, Seo DC, Lee MA. Clinical usefulness of
  • real-time PCR and amplicor MTB PCR assays for diagnosis of tuberculosis. Korean J Clin Microbiol. 2008; 11:29–33.
  • Piersimoni C, Scarparo C. Relevance of commercial amplification
  • methods for direct detection of Mycobacterium tuberculosis complex in clinical samples. J Clin Microbiol 2003;41:5355-5365.
  • Dinnes, J., et al.A systematic review of rapid diagnostic tests
  • for the detection of tuberculosis infection. Health Technol Assess
  • ;11:119–196.
  • Flores LL, Pai M, M. Colford J, et al. In-house nucleic acid amplification tests for the detection of Mycobacterium tuberculosisin
  • sputum specimens: meta-analysis and metaregression.BMC Microbiol 2005; 5:55.
  • Tan WY, Stratton CW. Diagnosis of Mycobacterium tuberculosis.
  • Advanced techniques in diagnostic microbiology, 2nd Edition. Springer Newyork Heidelberg Dordrecht, London 2006;567.
  • Kubica GPW, Dye E, Cohn ML, Middlebrook G. Sputum digestion
  • and decontamination with N-acetyl-Lcysteine- sodium hydroxide for culture of mycobacteria. Am Rev Respir Dis 1963; 87:775-779.
  • Waard JH, Robledo. Conventional diagnostic methods. In:
  • Palomino JC, Leão SC, Ritacco V (editors). Tuberculosis (Available from: www.TuberculosisTextbook.com). 2007;12:401-424.
  • Tuberculosis Division, International Union Against Tuberculosis
  • and Lung Disease. Tuberculosis bacteriology- priorities and indications in high prevalence countries: position of the technical staff of the Tuberculosis Division of the International Union Against. Int J Tuberc Lung Dis 2005; 9:355-361.
  • Telenti A, Marchesi F, Balz M, et al. Rapid identification of mycobacteria to the species level by polymerase chain reaction
  • and restriction enzyme analysis. J Clin Microbiol 1993;31:175–178.
  • Vincent V, Brown-Elliott BA, Jost KC, Wallace RJ. Mycobacterium:
  • phenotypic and genotypic identification, In Murray P. R., Baron E. J., Baron E. J., Pfaller M. A., Yolken R. H., editors.(ed.), Manual of clinical microbiology, 8th ed. American Society for Microbiology, Washington, DC.2003; p. 560–584.
  • Amplied MTD Test (amplified Mycobacterium tuberculosis
  • direct test for in vitro diagnostic use) [package insert] San Diego, CA: Gen-Probe 2001.
  • MagNA Pure LC Total Nucleic Acid Isolation Kit (Available
  • from:www.http://www.roche-applied-cience.com/shop/products/magna-pure-lc-total-nucleic-acid-isolation-kit)
  • Roche Molecular Systems, Inc, COBAS TaqMan MTB test
  • (2007) Roche Molecular Systems, Inc., Branchburg, NJ.
  • Biorad iCycler iQ™. Real-Time PCR Detection System. Instruction
  • Manual. Catalog Number: 170-8740.
  • Applied Biosystems, TaqMan® Universal PCR Master Mix,
  • Instruction Manual. Available from: www.appliedbiosystems.com
  • The LightCycler® 480 Real-Time PCR System Guide (2008)
  • Roche Applied Science, 68298 Mannheim, Germany, Roche
  • Diagnostics.
  • Rotor-Gene® Q and artus® PCR Kits -Pure Pathogen Detection
  • (2010) Available from: www.qiagen.com
  • AdvanSure TB/NTM real-time PCR kit procedures, LG Life
  • Sciences, Seul, Korea
  • Gardner MJ, Altman DG (ed.) Statistics with confidence. BMJ
  • Publishing Group, London, United Kingdom. 1989.
  • Gamboa F, Manterola JM, Lonca J, et al. Comparative evaluation
  • of two commercial assays for direct detection of Mycobacterium
  • tuberculosis in respiratory specimens. Eur J Clin Microbiol Infect Dis 1998; 17:151–156.
  • Kim YJ, Park MY, Kim SY, et al. Evaluation of the performances
  • of advanSure TB/NTM real time PCR Kit for detection of mycobacteria in respiratory specimens. Korean J Lab Med 2008; 28:34–38.
  • Yang YC, Lu PL, Huang SC, et al. Evaluation of the Cobas Taq Man MTB test for direct detection of Mycobacterium tuberculosis
  • complex in respiratory specimens. J Clin Microbiol 2011; 49(3):797-801. doi: 10.1128/JCM.01839-10.
  • Kim JH, Kim YJ, Ki CS, et al. Evaluation of COBAS TaqMan MTB PCR for detection of Mycobacterium tuberculosis. J Clin Microbiol 2011; 49:173–176.
There are 99 citations in total.

Details

Primary Language English
Journal Section Brief Report
Authors

Gülnur Tarhan This is me

Salih Cesur

Hülya Şimşek This is me

Ismail Ceyhan This is me

Yusuf Ozay This is me

Melike Atasever This is me

Publication Date February 6, 2016
Published in Issue Year 2015 Volume: 5 Issue: 3

Cite

APA Tarhan, G., Cesur, S., Şimşek, H., Ceyhan, I., et al. (2016). Diagnostic value of nine nucleic acid amplification test systems for Mycobacterium tuberculosis complex. Journal of Microbiology and Infectious Diseases, 5(3), 103-109. https://doi.org/10.5799/ahinjs.02.2015.03.0186
AMA Tarhan G, Cesur S, Şimşek H, Ceyhan I, Ozay Y, Atasever M. Diagnostic value of nine nucleic acid amplification test systems for Mycobacterium tuberculosis complex. J Microbil Infect Dis. February 2016;5(3):103-109. doi:10.5799/ahinjs.02.2015.03.0186
Chicago Tarhan, Gülnur, Salih Cesur, Hülya Şimşek, Ismail Ceyhan, Yusuf Ozay, and Melike Atasever. “Diagnostic Value of Nine Nucleic Acid Amplification Test Systems for Mycobacterium Tuberculosis Complex”. Journal of Microbiology and Infectious Diseases 5, no. 3 (February 2016): 103-9. https://doi.org/10.5799/ahinjs.02.2015.03.0186.
EndNote Tarhan G, Cesur S, Şimşek H, Ceyhan I, Ozay Y, Atasever M (February 1, 2016) Diagnostic value of nine nucleic acid amplification test systems for Mycobacterium tuberculosis complex. Journal of Microbiology and Infectious Diseases 5 3 103–109.
IEEE G. Tarhan, S. Cesur, H. Şimşek, I. Ceyhan, Y. Ozay, and M. Atasever, “Diagnostic value of nine nucleic acid amplification test systems for Mycobacterium tuberculosis complex”, J Microbil Infect Dis, vol. 5, no. 3, pp. 103–109, 2016, doi: 10.5799/ahinjs.02.2015.03.0186.
ISNAD Tarhan, Gülnur et al. “Diagnostic Value of Nine Nucleic Acid Amplification Test Systems for Mycobacterium Tuberculosis Complex”. Journal of Microbiology and Infectious Diseases 5/3 (February 2016), 103-109. https://doi.org/10.5799/ahinjs.02.2015.03.0186.
JAMA Tarhan G, Cesur S, Şimşek H, Ceyhan I, Ozay Y, Atasever M. Diagnostic value of nine nucleic acid amplification test systems for Mycobacterium tuberculosis complex. J Microbil Infect Dis. 2016;5:103–109.
MLA Tarhan, Gülnur et al. “Diagnostic Value of Nine Nucleic Acid Amplification Test Systems for Mycobacterium Tuberculosis Complex”. Journal of Microbiology and Infectious Diseases, vol. 5, no. 3, 2016, pp. 103-9, doi:10.5799/ahinjs.02.2015.03.0186.
Vancouver Tarhan G, Cesur S, Şimşek H, Ceyhan I, Ozay Y, Atasever M. Diagnostic value of nine nucleic acid amplification test systems for Mycobacterium tuberculosis complex. J Microbil Infect Dis. 2016;5(3):103-9.

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