Monitoring quality indicators for the Xpert MTB/RIF molecular assay in Ethiopia

Autoři: Abebaw Kebede aff001;  Dereje Beyene aff002;  Bazezew Yenew aff001;  Getu Diriba aff001;  Zemedu Mehamd aff001;  Ayinalem Alemu aff001;  Misikr Amare aff001;  Gobena Ameni aff003
Působiště autorů: Ethiopian Public Health Institute, Addis Ababa, Ethiopia aff001;  Department of Microbial, Cellular and Molecular Biology, College of Natural and Computational Sciences, Addis Ababa University, Addis Ababa, Ethiopia aff002;  Aklilu Lemma Institute of Pathology, Addis Ababa University, Addis Ababa, Ethiopia aff003
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225205



In Ethiopia, >300 GeneXpert instruments have been deployed for tuberculosis (TB) testing using the Xpert MTB/RIF cartridge. Implementing quality indicators is necessary for monitoring and evaluating the quality of Xpert MTB/RIF diagnostic services.


To assess the use of quality indicators for the Xpert MTB/RIF molecular assay in Ethiopia and to compare the findings with the predefined targets described in the literature.


Clinical specimens collected from patients with suspected TB were subjected to Xpert MTB/RIF testing at the National TB Reference Laboratory (NTRL) between January and December 2018. Data were collected from GeneXpert software and Laboratory Information System (LIS) databases. Quality indicators were calculated and analyzed. Bivariate and multivariate analyses were performed using SPSS software version 20 (SPSS Inc., Chicago, Illinois, USA).


Of the 2515 specimens tested, 2274 (90.4%) had successful test results; 18.2% were positive for Mycobacterium tuberculosis (MTB). Among MTB positives (n = 413), 4.8% and 1.0% were rifampicin (RIF)-resistant and RIF-indeterminate cases, respectively. Unsuccessful results were 241 (9.6%); 8.9% of the total number of tests were errors, 0.04% had invalid results and 0.6% ‘no result’. The most frequent error was probe check failure (error 5007). Instrument module A4, B2, B3, C3, and D3 (p<0.05) and tester experience (p<0.05) had a statistically significant association with errors in multivariate analysis. Additional 42 MTB cases (9.2% of the total cases) were detected among unsuccessful results by follow-up tests. Sixty-four percent of the initial test results were released within the turnaround time (TAT) ≤24 hours.


Most of the quality indicators for the Xpert MTB/RIF molecular assay were maintained within the targets. However, the error rate and TAT were out of the targets. Defective modules and lacking experience were the factors affecting successful test outcomes.

Klíčová slova:

Ethiopia – Government laboratories – Polymerase chain reaction – Specimen preparation and treatment – Sputum – Tuberculosis


1. Evans CA. GeneXpert—a game-changer for tuberculosis control? PLoS medicine. 2011;8(7):e1001064. doi: 10.1371/journal.pmed.1001064 21814497

2. World Health Organization., Xpert MTB/RIF implementation manual: technical and operational ‘how-to’; practical considerations. WHO; 2014.

3. World Health Organization., Automated Real-Time Nucleic Acid Amplification Technology for Rapid and Simultaneous Detection of Tuberculosis and Rifampicin Resistance: Xpert MTB/RIF Assay for the Diagnosis of Pulmonary and Extrapulmonary TB in Adults and Children: Policy Update WHO, 2013.

4. FMOH. Implementation guideline for GeneXpert MTB/RIF assay in Ethiopia. Federal Democratic Republic of Ethiopia, Ministry of Health, Addis Ababa, Ethiopia; 2014.

5. FMOH. National Guidelines for TB, DR-TB and Leprosy in Ethiopia. Federal Democratic Republic of Ethiopia, Ministry of Health, Addis Ababa, Ethiopia; August 2018.

6. Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, et al. Rapid molecular detection of tuberculosis and rifampin resistance. New England Journal of Medicine. 2010;363(11):1005–15. doi: 10.1056/NEJMoa0907847 20825313

7. ISO 15189: Medical laboratories—Particular requirements for quality and competence.: International Organization for Standardization, Geneva, Switzerland; 2012.

8. Selvakumar N, Silambuchelvi K, Sekar MG, Sunder AS, Anbarasu S, Rekha VB, et al. Quality indicators in a mycobacteriology laboratory supporting clinical trials for pulmonary tuberculosis. International journal of mycobacteriology. 2012;1(4):185–9. doi: 10.1016/j.ijmyco.2012.09.004 26785621

9. McCarthy K, Metchock B, Kanphukiew A, Monkongdee P, Sinthuwattanawibool C, Tasaneeyapan T, et al. Monitoring the performance of mycobacteriology laboratories: a proposal for standardized indicators. The International Journal of Tuberculosis and Lung Disease. 2008;12(9):1015–20. 18713498

10. Maronna A, Souza RA, Montes FCO. Description of the quality indicators defined in the National Reference Laboratory in Tuberculosis of CRPHF/Ensp/Fiocruz by means of the process mapping methodology. Jornal Brasileiro de Patologia e Medicina Laboratorial. 2017;53(3):165–76.

11. Global Laboratory Initiative., GLI practical guide to TB laboratory strengthening. 2017.

12. World Health Organization., Global tuberculosis report 2018. Geneva, Switzerland: WHO, 2018.

13. Geleta DA, Megerssa YC, Gudeta AN, Akalu GT, Debele MT, Tulu KD. Xpert MTB/RIF assay for diagnosis of pulmonary tuberculosis in sputum specimens in remote health care facility. BMC microbiology. 2015;15(1):220.

14. Jaleta KN, Gizachew M, Gelaw B, Tesfa H, Getaneh A, Biadgo B. Rifampicin-resistant Mycobacterium tuberculosis among tuberculosis-presumptive cases at University of Gondar Hospital, northwest Ethiopia. Infection and drug resistance. 2017;10:185. doi: 10.2147/IDR.S135935 28652786

15. Mulu W, Abera B, Yimer M, Hailu T, Ayele H, Abate D. Rifampicin-resistance pattern of Mycobacterium tuberculosis and associated factors among presumptive tuberculosis patients referred to Debre Markos Referral Hospital, Ethiopia: a cross-sectional study. BMC research notes. 2017;10(1):8. doi: 10.1186/s13104-016-2328-4 28057041

16. Arega B, Menbere F, Getachew Y. Prevalence of rifampicin resistant Mycobacterium tuberculosis among presumptive tuberculosis patients in selected governmental hospitals in Addis Ababa, Ethiopia. BMC infectious diseases. 2019;19(1):307. doi: 10.1186/s12879-019-3943-1 30947695

17. Derbie A, Worku S, Mekonnen D, Mezgebu Y, Teshager A, Birhan A, et al. Xpert MTB/RIF assay for the diagnosis of Mycobacterium tuberculosis and its Rifampicin resistance at Felege Hiwot and Debre Tabor Hospitals, Northwest Ethiopia: A preliminary implementation research. Ethiopian Journal of Health Development. 2016;30(2):60–6.

18. Gelalcha AG, Kebede A, Mamo H. Light-emitting diode fluorescent microscopy and Xpert MTB/RIF® assay for diagnosis of pulmonary tuberculosis among patients attending Ambo hospital, west-central Ethiopia. BMC infectious diseases. 2017;17(1):613. doi: 10.1186/s12879-017-2701-5 28893193

19. Bodmer T, Ströhle A. Diagnosing pulmonary tuberculosis with the Xpert MTB/RIF test. Journal of visualized experiments: JoVE. 2012;(62).

20. GeneXpert Dx System Operator Manual. Software Version 4. Sunnyvale, CA, USA: Cepheid Inc; 2012.

21. 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? European Respiratory Journal. 2016;48(2):516–25. doi: 10.1183/13993003.00543-2016 27418550

22. Agonafir M, Assefa Y, Girmachew F, Jerene D. Factors affectinsg the utilization of Xpert MTB/RIF assay among TB clinic health workers in Addis Ababa. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases. 2018;12:48–53.

23. Assefa D, Belachew F, Wondimagegn G, Klinkenberg E. Missed pulmonary tuberculosis: a cross sectional study in the general medical inpatient wards of a large referral hospital in Ethiopia. BMC infectious diseases. 2019;19(1):60. doi: 10.1186/s12879-019-3716-x 30654763

24. Kebede A, Alebachew Z, Tsegaye F, Lemma E, Abebe A, Agonafir M, et al. The first population-based national tuberculosis prevalence survey in Ethiopia, 2010–2011. The International Journal of Tuberculosis and Lung Disease. 2014;18(6):635–9. doi: 10.5588/ijtld.13.0417 24903931

25. Datiko DG, Guracha EA, Michael E, Asnake G, Demisse M, Theobald S, et al. Sub-national prevalence survey of tuberculosis in rural communities of Ethiopia. BMC public health. 2019;19(1):295. doi: 10.1186/s12889-019-6620-9 30866870

26. Berhe G, Enqueselassie F, Hailu E, Mekonnen W, Teklu T, Gebretsadik A, et al. Population-based prevalence survey of tuberculosis in the Tigray region of Ethiopia. BMC infectious diseases. 2013;13(1):448.

27. WHO. Global tuberculosis report 2018: World Health Organization; 2018.

28. Eshetie S, Moges F, Dagnew M. Multidrug-resistant tuberculosis in Ethiopian settings and its association with previous antituberculosis treatment: A systematic review and meta-analysis. International journal of mycobacteriology. 2016;5:S119–S20. doi: 10.1016/j.ijmyco.2016.09.022 28043498

29. Creswell J, Codlin AJ, Andre E, Micek MA, Bedru A, Carter EJ, et al. Results from early programmatic implementation of Xpert MTB/RIF testing in nine countries. BMC infectious diseases. 2014;14(1):2.

30. Gidado M, Nwokoye N, Nwadike P, Ajiboye P, Eneogu R, Useni S, et al. Unsuccessful Xpert® MTB/RIF results: the Nigerian experience. Public health action. 2018;8(1):2–6. doi: 10.5588/pha.17.0080 29581936

31. Agizew T, Boyd R, Ndwapi N, Auld A, Basotli J, Nyirenda S, et al. Peripheral clinic versus centralized laboratory-based Xpert MTB/RIF performance: Experience gained from a pragmatic, stepped-wedge trial in Botswana. PloS one. 2017;12(8):e0183237. doi: 10.1371/journal.pone.0183237 28817643

32. Ardizzoni E, Fajardo E, Saranchuk P, Casenghi M, Page A-L, Varaine F, et al. Implementing the Xpert® MTB/RIF diagnostic test for tuberculosis and rifampicin resistance: outcomes and lessons learned in 18 countries. PLoS One. 2015;10(12):e0144656. doi: 10.1371/journal.pone.0144656 26670929

33. Mustapha G, Jumoke O, Nwadike P, Emeka E, Akang G, Eneogu R, et al. Assessment of Gene-xpert MTB RIF program implementation and the challenges for enhanced tuberculosis diagnosis in Nigeria. SAARC Journal of Tuberculosis, Lung Diseases and HIV/AIDS. 2015;12(2):1–7.

34. FIND Report., Performance of Xpert MTB/RIF version G4 assay. Geneva, Switzerland: Foundation for Innovative New Diagnostics, 2011. Available from:

35. 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. Journal of clinical microbiology. 2010;48(7):2495–501. doi: 10.1128/JCM.00128-10 20504986

36. Akane A, Matsubara K, Nakamura H, Takahashi S, Kimura K. Identification of the heme compound copurified with deoxyribonucleic acid (DNA) from bloodstains, a major inhibitor of polymerase chain reaction (PCR) amplification. Journal of Forensic Science. 1994;39(2):362–72.

37. Al-Soud WA, Rådström P. Purification and characterization of PCR-inhibitory components in blood cells. Journal of clinical microbiology. 2001;39(2):485–93. doi: 10.1128/JCM.39.2.485-493.2001 11158094

38. Shiferaw MB, Yismaw G. Magnitude of delayed turnaround time of laboratory results in Amhara Public Health Institute, Bahir Dar, Ethiopia. BMC health services research. 2019;19(1):240. doi: 10.1186/s12913-019-4077-2 31014324

Článek vyšel v časopise


2019 Číslo 11