Diagnostic accuracy of Xpert MTB/RIF assay and non-molecular methods for the diagnosis of tuberculosis lymphadenitis


Autoři: Mengistu Fantahun aff001;  Abebaw Kebede aff003;  Bazezew Yenew aff003;  Tufa Gemechu aff004;  Yeshiwondm Mamuye aff002;  Mengistu Tadesse aff003;  Bereket Brhane aff001;  Aisha Jibriel aff001;  Dawit Solomon aff001;  Zelalem Yaregal aff003
Působiště autorů: Pathology, St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia aff001;  Department of Microbiology, St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia aff002;  Ethiopian Public Health Institution, Addis Ababa Ethiopia aff003;  Pathology, Addis Ababa University, Addis Ababa, Ethiopia aff004
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222402

Souhrn

Background

Tuberculous lymphadenitis (TBLN) diagnosis remains a challenge in resource limited countries like Ethiopia. Most diagnostic centers in Ethiopia use smear microscopy, but it has low sensitivity in detecting tubercle bacilli in fine needle aspiration (FNA) specimens. FNA cytology (FNAC) is another widely applicable diagnostic option but it has low specificity for diagnosing TBLN. In 2014, WHO recommended Xpert MTB/RIF assay to be used in detecting TB from FNA specimen by considering the diagnostic limitations of microscopy and cytology. In Ethiopia, there is limited data on Xpert MTB/RIF performance in detecting TBLN from FNA. Therefore, this study aimed to evaluate the diagnostic performance of Xpert MTB/RIF assay and non-molecular methods (cytology, microscopy and culture) for the diagnosis of TBLN.

Methods

A cross-sectional study was conducted on 152 presumptive TBLN patients at St. Paul’s Hospital Millennium Medical College (SPHMMC) from December 2015 to May 2016 in Addis Ababa, Ethiopia. FNA specimens were collected from each patient. Individual patient specimens were examined by microscopy (acid fast and auramine O staining), cytology, Xpert MTB/RIF and culture. Each specimen was directly inoculated and its sediment following decontamination procedure onto two duplicate Löwenstein-Jensen (LJ) media. Composite culture (specimen positive by direct or concentrated or both culturing methods) and composite method (positive by either one of the non-molecular methods) were taken as reference methods. The data was captured and analyzed using software packages SPSS version 20 (SPSS Inc, Chicago, Illinois, USA). Sensitivity, specificity, positive predictive value, and negative predictive value were calculated.

Result

A total of 152 presumptive TBLN patients were enrolled in this study. Of these, 105(69%), 68(44.7%), 64(42%), 48(32%) and 33(22%) were positive for M. tuberculosis using composite method (positive by either one of the non-molecular method), composite culture, direct, and concentrated culture, respectively. TB positivity rate was 67.8%, 49.3%, 24.3%, and 14.5% using cytology, Xpert MTB/RIF, Auramine O (FM) microscopy, and Ziehl Nelson (ZN) microscopy, respectively. Using composite culture as reference, the sensitivity and specificity of Xpert MTB/RIF was 78% (95% CI: 73.7% to 82.3%) and 74% (95%CI: 69.4% to 78.6%), respectively. However, the sensitivity of Xpert MTB/RF improved from 78% to 92% using composite method as a reference. The high positivity rate observed in purulent (70%) followed by caseous (66.7%) type of aspirates by Xpert MTB/RIF.

Conclusion

Xpert MTB/RIF assay has both considerable sensitivity and specificity; it may be employed for better diagnosis, management and treatment of presumptive TBLN patients.

Klíčová slova:

Biology and life sciences – Cell biology – Cytology – Organisms – Bacteria – Actinobacteria – Mycobacterium tuberculosis – Medicine and health sciences – Infectious diseases – Bacterial diseases – Tuberculosis – Tropical diseases – Diagnostic medicine – Tuberculosis diagnosis and management – Research and analysis methods – Specimen preparation and treatment – Staining – Acid-fast stain – Microscopy – Light microscopy – Fluorescence microscopy


Zdroje

1. World Health Organization. Global Tuberculosis Control 2014. Geneva, Switzerland:who.int/tb/publications/global report/

2. Biadglegne F., Tesfaye W., Anagaw B., Tessema B., Debebe T., Anagaw, et al, 2013. Tuberculosis lymphadenitis in Ethiopia. Japanese journal of infectious diseases, 66(4), pp.263–268. 23883834

3. Muluye D., Biadgo B., Woldegerima E. and Ambachew A., 2013. Prevalence of tuberculous lymphadenitis in Gondar University Hospital, Northwest Ethiopia. BMC Public Health, 13(1), p.435.

4. Biadglegne F., Tesfaye W., Sack U. and Rodloff A.C., 2013. Tuberculous lymphadenitis in northern Ethiopia: in a public health and microbiological perspectives. PLoS One, 8(12), p.e81918. doi: 10.1371/journal.pone.0081918 24349151

5. World Health Organization, 2018. Global tuberculosis report 2018. World Health Organization.

6. Aguado J.M. and Castrillo J.M., 1987. Lymphadenitis as a characteristic manifestation of disseminated tuberculosis in intravenous drug abusers infected with human immunodeficiency virus. Journal of Infection, 14(2), pp.191–193. doi: 10.1016/s0163-4453(87)92177-3 3572022

7. Honore-Bouakline S., Vincensini J.P., Giacuzzo V., Lagrange P.H. and Herrmann J.L., 2003. Rapid diagnosis of extrapulmonary tuberculosis by PCR: impact of sample preparation and DNA extraction. Journal of clinical microbiology, 41(6), pp.2323–2329. doi: 10.1128/JCM.41.6.2323-2329.2003 12791844

8. Ergete W. and Bekele A., 2000. Acid fast bacilli in aspiration smears from tuberculous patients. Ethiopian Journal of Health Development, 14(1), pp.99–104.

9. Steingart K.R., Henry M., Ng V., Hopewell P.C., Ramsay A., Cunningham J., et al, 2006. Fluorescence versus conventional sputum smear microscopy for tuberculosis: a systematic review. The Lancet infectious diseases, 6(9), pp.570–581. doi: 10.1016/S1473-3099(06)70578-3 16931408

10. Grange J.M., 1989. The rapid diagnosis of paucibacillary tuberculosis. Tubercle, 70(1), pp.1–4. doi: 10.1016/0041-3879(89)90059-7 2675426

11. Moure R., Martín R. and Alcaide F., 2012. Effectiveness of an integrated real-time PCR method for detection of the Mycobacterium tuberculosis complex in smear-negative extrapulmonary samples in an area of low tuberculosis prevalence. Journal of clinical microbiology, 50(2), pp.513–515. doi: 10.1128/JCM.06467-11 22162564

12. Bezabih M., Mariam D.W. and Selassie S.G., 2002. Fine needle aspiration cytology of suspected tuberculous lymphadenitis. Cytopathology, 13(5), pp.284–290. 12421444

13. Gupta A.K., Nayar M. and Chandra M.I.T.H.I.L.E.S.H., 1992. Critical appraisal of fine needle aspiration cytology in tuberculous lymphadenitis. Acta cytologica, 36(3), pp.391–394. 1580124

14. Radhika S., Gupta S.K., Chakrabarti A., Rajwanshi A. and Joshi K., 1989. Role of culture for mycobacteria in fine‐needle aspiration diagnosis of tuberculous lymphadenitis. Diagnostic cytopathology, 5(3), pp.260–262. doi: 10.1002/dc.2840050306 2507267

15. Chao S.S., Loh K.S., Tan K.K. and Chong S.M., 2002. Tuberculous and nontuberculous cervical lymphadenitis: a clinical review. Otolaryngology—Head and Neck Surgery, 126(2), pp.176–179. doi: 10.1067/mhn.2002.121912 11870349

16. Derese Y., Hailu E., Assefa T., Bekele Y., Mihret A., Aseffa A., et al, 2012. Comparison of PCR with standard culture of fine needle aspiration samples in the diagnosis of tuberculosis lymphadenitis. The Journal of Infection in Developing Countries, 6(01), pp.53–57.

17. World Health Organization, 2011. Rapid implementation of the Xpert MTB/RIF diagnostic test: technical and operational'How-to'; practical considerations (No. WHO/HTM/TB/2011.2). Geneva: World Health Organization.

18. World Health Organization ed., 2013. Global tuberculosis report 2013. World Health Organization.

19. World Health Organization, 2013. Automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: XpertMTB(No. WHO/HTM/TB/2013.16). World Health Organization.

20. Al-Ateah S.M., Al-Dowaidi M.M. and El-Khizzi N.A., 2012. Evaluation of direct detection of Mycobacterium tuberculosis complex in respiratory and non-respiratory clinical specimens using the Cepheid Gene Xpert® system. Saudi medical journal, 33(10), pp.1100–1105. 23047207

21. Biadglegne F., Mulu A., Rodloff A.C. and Sack U., 2014. Diagnostic performance of the Xpert MTB/RIF assay for tuberculous lymphadenitis on fine needle aspirates from Ethiopia. Tuberculosis, 94(5), pp.502–505. doi: 10.1016/j.tube.2014.05.002 24931451

22. Hillemann D., Rüsch-Gerdes S., Boehme C. and Richter E., 2011. Rapid molecular detection of extrapulmonary tuberculosis by the automated GeneXpert MTB/RIF system. Journal of clinical microbiology, 49(4), pp.1202–1205. doi: 10.1128/JCM.02268-10 21270230

23. World Health Organization, 2014. Xpert MTB/RIF implementation manual: technical and operational ‘how-to’; practical considerations (No. WHO/HTM/TB/2014.1). World Health Organization.

24. Nataraj G., Kurup S., Pandit A. and Mehta P., 2002. Correlation of fine needle aspiration cytology, smear and culture in tuberculous lymphadenitis: a prospective study. Journal of postgraduate Medicine, 48(2), p.113. 12215692

25. Mohapatra P.R. and Janmeja A.K., 2009. Tuberculous lymphadenitis. J Assoc Physicians India, 57(6), pp.585–90.

26. Reddy V.K., Aparna S., Prasad C.E., Srinivas A., Triveni B., Gokhale S. et al, 2008. Mycobacterial culture of fine needle aspirate-A useful tool in diagnosing tuberculous lymphadenitis. Indian Journal of medical microbiology, 26(3), p.259. 18695328

27. Annam V., Karigoudar M.H. and Yelikar B.R., 2009. Improved microscopical detection of acid-fast bacilli by the modified bleach method in lymphnode aspirates. Indian Journal of Pathology and Microbiology, 52(3), p.349. doi: 10.4103/0377-4929.54991 19679958

28. World Health Organization, 2011. Fluorescent light-emitting diode (LED) microscopy for diagnosis of tuberculosis: policy statement (No. WHO/HTM/TB/2011.8). Geneva: World Health Organization.

29. Tadesse M., Abebe G., Abdissa K., Aragaw D., Abdella K., Bekele A., et al, 2015. GeneXpert MTB/RIF assay for the diagnosis of tuberculous lymphadenitis on concentrated fine needle aspirates in high tuberculosis burden settings. PLOS one, 10(9), p.e0137471. doi: 10.1371/journal.pone.0137471 26366871

30. Buli G.A., Lukas F.Y. and Amenta N.W., 2015. Magnitude of Tuberculosis Lymphadenitis in Hawassa University referral hospital, Southern Ethiopia. Am. J. Pharm. Health Res, 3(2), pp.116–120.

31. Denkinger C.M., Schumacher S.G., Boehme C.C., Dendukuri N., Pai M. and Steingart K.R., 2014. Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis. European Respiratory Journal, 44(2), pp.435–446. doi: 10.1183/09031936.00007814 24696113

32. Tadesse M., Abebe G., Abdissa K., Aragaw D., Abdella K., Bekele A.,et al, 2015. GeneXpert MTB/RIF assay for the diagnosis of tuberculous lymphadenitis on concentrated fine needle aspirates in high tuberculosis burden settings. PLOS one, 10(9), p.e0137471. doi: 10.1371/journal.pone.0137471 26366871

33. Garedew L., Mihret A., Abebe T. and Ameni G., 2013. Molecular typing of mycobacteria isolated from extrapulmonary tuberculosis patients at Debre Birhan Referral Hospital, central Ethiopia. Scandinavian journal of infectious diseases, 45(7), pp.512–518. doi: 10.3109/00365548.2013.773068 23477546

34. Zewdie O., Abebe T., Mihret A., Hirpa E. and Ameni G., 2017. Concentration of fine needle aspirates similar to molecular method improves sensitivity of the diagnosis of tuberculous lymphadenitis in Addis Ababa, Ethiopia. BMC infectious diseases, 17(1), p.77. doi: 10.1186/s12879-017-2194-2 28088186

35. Mittal P., Handa U., Mohan H. and Gupta V., 2011. Comparative evaluation of fine needle aspiration cytology, culture, and PCR in diagnosis of tuberculous lymphadenitis. Diagnostic cytopathology, 39(11), pp.822–826. doi: 10.1002/dc.21472 21994193

36. Mistry Y., Ninama G.L., Mistry K., Rajat R., Parmar R. and Godhani A., 2012. Efficacy of fine needle aspiration cytology, Ziehl-Neelsen stain and culture (Bactec) in diagnosis of tuberculosis lymphadenitis. Natl J Med Res, 2, pp.77–80.

37. Ageep A.K., 2012. Diagnosis of tuberculous lymphadenitis in Red Sea state, Sudan. International Journal of Tropical Medicine, 7(1), pp.53–56.

38. Nidhi P., Sapna T., Shalini M. and Kumud G., 2011. FNAC in tuberculous lymphadenitis: Experience from a tertiary level referral centre. Indian J Tuberc, 58(3), pp.102–107. 21941948

39. Fanny M.L., Beyam N., Gody J.C., Zandanga G., Yango F., Manirakiza A., et al, 2012. Fine-needle aspiration for diagnosis of tuberculous lymphadenitis in children in Bangui, Central African Republic. BMC pediatrics, 12(1), p.191.

40. Iwnetu R., Van Den Hombergh J., Woldeamanuel Y., Asfaw M., Gebrekirstos C., Negussie Y., et al 2009. Is tuberculous lymphadenitis over-diagnosed in Ethiopia? Comparative performance of diagnostic tests for mycobacterial lymphadenitis in a high-burden country. Scandinavian journal of infectious diseases, 41(6–7), pp.462–468. doi: 10.1080/00365540902897697 19382003

41. Abdissa K., Tadesse M., Bezabih M., Bekele A., Apers L., Rigouts L. et al, 2014. Bacteriological methods as add on tests to fine-needle aspiration cytology in diagnosis of tuberculous lymphadenitis: can they reduce the diagnostic dilemma?. BMC infectious diseases, 14(1), p.720.


Článek vyšel v časopise

PLOS One


2019 Číslo 9

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Výhody léčby pacientů s DM 2. typu GLP-1 agonisty
nový kurz
Autoři: prof. MUDr. Martin Haluzík, DrSc.

Syndrom suchého oka – diagnostika, komplikace a léčba
Autoři: MUDr. Petr Výborný, CSc., FEBO

Systémová léčba psoriázy
Autoři: MUDr. Jiří Horažďovský, Ph.D

Klinická farmakokinetika betablokátorů
Autoři:

Současné možnosti terapie osteoartrózy
Autoři: MUDr. Jakub Holešovský

Všechny kurzy
Kurzy Doporučená témata