Comparison of GeneXpert MTB to Mycobacterium tuberculosis culture in children with tuberculosis
Abstract
Background Diagnosing tuberculosis (TB) in children is difficult. Typical methods take a long time to achieve results, or have a low sensitivity. GeneXpert is a nucleic acid amplification test used to identify Mycobacterium tuberculosis bacteria (MTB) in only 2 hours.
Objective To compare the sensitivity and specificity of GeneXpert MTB to MTB culture in children with TB, and to assess factors associated with GeneXpert MTB test in predicting which children were likely to have positive results.
Methods This descriptive, analytical study was done in children with suspected TB, aged 1 month to 18 years in Hasan Sadikin Hospital, Bandung, West Java, from January 2016 to December 2017. The data were taken from the medical records and included age, gender, nutritional status, symptoms of TB, chest x-ray, and tuberculin test results. The GeneXpert MTB test was compared to cultures from the same patient, with regards to sensitivity, specificity, and agreement using Kappa index. We analyzed factors associated to GeneXpert MTB test using logistic regression analysis.
Results From 454 inpatients and 1,750 outpatients with suspected TB, there were 251 children who were tested by MTB culture and 722 children tested by GeneXpert MTB. Of the 70 cases who met the inclusion criteria and underwent both tests, factors associated with positive GeneXpert MTB results were age 10 to 18 years, female gender, and positive tuberculin skin test (TST). The GeneXpert MTB test showed sensitivity 78.9% (95%CI 56.7 to 91.5) and specificity 86.3% (95%CI 74.3 to 93.2), with accuracy of 84.3% (95%CI 74 to 91), and agreement value of Æ™=0.62 (95%CI 41.6 to 82.7).
Conclusion Specificity of GeneXpert MTB is higher than its sensitivity compared to TB cultures in children. The tests were in good agreement. Age 10 to 18 years had the strongest association with positive GeneXpert MTB results.
References
2. Elhassan MM, Elmekki MA, Osman AL, Hamid ME. Challenges in diagnosing tuberculosis in children: a comparative study from Sudan. Int J Infect Dis. 2016;43:25–9.
3. Swaminathan S, Rekha B. Pediatric tuberculosis: global overview and challenges. Clin Infect Dis. 2010;50:S184–94.
4. Detjen AK, DiNardo AR, Leyden J, Steingart KR, Menzies D, Schiller I, et al. Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in children: a systematic review and meta-analysis. Lancet Respir Med. 2015;3:451–61.
5. Lighter J, Riguaud M. Diagnosis childhood tuberculosis: traditional and innovative modalities. Curr Probl Pediatr Adolesc Health Care. 2009;39:61–88.
6. Nicol MP, Workman L, Isaacs W, Munro J, Black F, Eley B, et al. Accuracy of the Xpert MTB/RIF test for the diagnosis of pulmonary tuberculosis in children admitted to hospital in Cape Town, South Africa: a descriptive study. Lancet Infect Dis. 2011;11:819–24.
7. Sekadde MP, Wobudeya E, Joloba ML, Ssengooba W, Kisembo H, Bakeera-Kitaka S, et al. Evaluation of the Xpert MTB/RIF test for the diagnosis of childhood pulmonary tuberculosis in Uganda: a cross-sectional diagnostic study. BMC Infect Dis. 2013;13:133.
8. Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, et al. Rapid molecular detection of tuberculosis and rifamipicin resistance. N Engl J Med. 2010;363:1005–15.
9. Hasan Z, Shakoor S, Arif F, Mehnaz A, Akber A, Haider M, et al. Evaluation of Xpert MTB/RIF testing for rapid diagnosis of childhood pulmonary tuberculosis in children by Xpert MTB/RIF testing of stool samples in a low resource setting. BMC Res Notes. 2017;10:473.
10. World Health Organization. Guidance for national tuberculosis programmes on the management of tuberculosis in children [Internet]. Geneva: World Health Organization; 2006 [cited 2018 March 1]. Available from http://whqlibdoc.who.int/hq/2006/WHO_HTM_TB_2006.371_eng.pdf
11. World Health Organization.Treatment of tuberculosis guidelines. Geneva: World Health Organization; 2009 [cited 2018 March 1]. Available from: http://whqlibdoc.who.int/publications/2010/9789241547833_eng.pdf
12. Mallinckrodt B, Abraham WT, Wei M, Russel DW. Advances in testing the statistical significance of mediation effects. J Couns Psychol. 2006;53:372–8.
13. Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC. Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. JAMA. 1999;282:677–86.
14. Zeka AN, Tasbakan S, Cavusoglo 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;49:4138–41.
15. 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 Infect Dis. 2013;13:507.
16. Moure R, Munoz L, Torres M, Santin M, Martin 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;49:1137–9.
17. Bunyasi EW, Tameris M, Geldenhyus H, Schmidt BM, Luabeya AK, Mulenga H, et al. Evaluation of Xpert MTB/RIF assay in induced sputum and gastric lavage samples from young children with suspected tuberculosis from the MVA85A TB vaccine trial. PLoS One. 2015;10:e0141623.
18. Tang T, Liu F, Lu X, Huang Q. Evaluation of GeneXpert MTB/RIF for detecting Mycobacterium tuberculosis in a hospital in China. J Int Med Res. 2017;45:816–22.
19. Hasan Z, Shakoor S, Arif F, Mehnaz A, Akber A, Halder M, et al. Evaluation of Xpert MTB/RIF testing for rapid diagnosis of childhood pulmonary tuberculosis in children by Xpert MTB/RIF testing of stool samples in a low resource setting. BMC Res Notes. 2017;10:473.
20. Li Y, Pang Y, Zhang T, Xian X, Wang X, Yang J, et al. Rapid diagnosis of extrapulmonary tuberculosis with Xpert Mycobacterium tuberculosis/rifampicin assay. J Med Microbiol. 2017;66:910–4.
21. Marais BJ, Gie RP, Schaaf HS, Hesseling AC, Obihara CC, Starke JJ, et al. The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era. Int J Tuberc Lung Dis. 2004;8:392-402.
22. Marais BJ, Gie RP, Hesseling AH, Beyers N. Adult type pulmonary tuberculosis in children 10–14 years of age. Pediatr Infect Dis J. 2005;24:743-4.
Copyright (c) 2019 Betty Agustina, Cissy Kartasasmita, Dany Hilmanto
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Authors who publish with this journal agree to the following terms:
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
Accepted 2019-04-29
Published 2019-05-02
