Xpert Ultra Assay on Stool to Diagnose Pulmonary Tuberculosis in Children

Senjuti Kabir, S M Mazidur Rahman, Shakil Ahmed, Md Shamiul Islam, Rupali Sisir Banu, Hemant Deepak Shewade, Pruthu Thekkur, Sayeeda Anwar, Nazneen Akhter Banu, Rumana Nasrin, Mohammad Khaja Mafij Uddin, Sabrina Choudhury, Shahriar Ahmed, Kishor Kumar Paul, Razia Khatun, Mohammod Jobayer Chisti, Sayera Banu, Senjuti Kabir, S M Mazidur Rahman, Shakil Ahmed, Md Shamiul Islam, Rupali Sisir Banu, Hemant Deepak Shewade, Pruthu Thekkur, Sayeeda Anwar, Nazneen Akhter Banu, Rumana Nasrin, Mohammad Khaja Mafij Uddin, Sabrina Choudhury, Shahriar Ahmed, Kishor Kumar Paul, Razia Khatun, Mohammod Jobayer Chisti, Sayera Banu

Abstract

Background: The World Health Organization recommends the Xpert MTB/RIF Ultra assay for diagnosing pulmonary tuberculosis (PTB) in children. Though stool is a potential alternative to respiratory specimens among children, the diagnostic performance of Xpert Ultra on stool is unknown. Thus, we assessed the diagnostic performance of Xpert Ultra on stool to diagnose PTB in children.

Methods: We conducted a cross-sectional study among consecutively recruited children (< 15 years of age) with presumptive PTB admitted in 4 tertiary care hospitals in Dhaka, Bangladesh, between January 2018 and April 2019. Single induced sputum and stool specimens were subjected to culture, Xpert, and Xpert Ultra. We considered children as bacteriologically confirmed on induced sputum if any test performed on induced sputum was positive for Mycobacterium tuberculosis and bacteriologically confirmed if M. tuberculosis was detected on either induced sputum or stool.

Results: Of 447 children, 29 (6.5%) were bacteriologically confirmed on induced sputum and 72 (16.1%) were bacteriologically confirmed. With "bacteriologically confirmed on induced sputum" as a reference, the sensitivity and specificity of Xpert Ultra on stool were 58.6% and 88.1%, respectively. Xpert on stool had sensitivity and specificity of 37.9% and 100.0%, respectively. Among bacteriologically confirmed children, Xpert Ultra on stool was positive in 60 (83.3%), of whom 48 (80.0%) had "trace call."

Conclusions: In children, Xpert Ultra on stool has better sensitivity but lesser specificity than Xpert. A high proportion of Xpert Ultra assays positive on stool had trace call. Future longitudinal studies on clinical evolution are required to provide insight on the management of children with trace call.

Keywords: SORT IT; Xpert; Xpert Ultra; childhood TB; stool.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Flowchart depicting the enrollment, investigation results, and treatment of children (

Figure 2.

Venn diagram depicting bacteriological confirmation…

Figure 2.

Venn diagram depicting bacteriological confirmation using culture, Xpert MTB/RIF, and Xpert MTB/RIF Ultra…

Figure 2.
Venn diagram depicting bacteriological confirmation using culture, Xpert MTB/RIF, and Xpert MTB/RIF Ultra assays on induced sputum and stool specimens from children (
Comment in
Similar articles
Cited by
References
    1. World Health Organization. Global tuberculosis report 2019. Geneva, Switzerland: WHO, 2019.
    1. Welday SH, Kimang’a AN, Kabera BM, et al. . Stool as appropriate sample for the diagnosis of Mycobacterium tuberculosis by Gene Xpert test. Open J Respir Dis 2014; 4:83.
    1. Banada PP, Naidoo U, Deshpande S, et al. . A novel sample processing method for rapid detection of tuberculosis in the stool of pediatric patients using the Xpert MTB/RIF assay. PLoS One 2016; 11:e0151980. - PMC - PubMed
    1. Khan EA, Starke JR. Diagnosis of tuberculosis in children: increased need for better methods. Emerg Infect Dis 1995; 1:115–23. - PMC - PubMed
    1. Dodd PJ, Gardiner E, Coghlan R, Seddon JA. Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study. Lancet Glob Health 2014; 2:e453–9. - PubMed
Show all 23 references
Publication types
MeSH terms
[x]
Cite
Copy Download .nbib .nbib
Format: AMA APA MLA NLM
Figure 2.
Figure 2.
Venn diagram depicting bacteriological confirmation using culture, Xpert MTB/RIF, and Xpert MTB/RIF Ultra assays on induced sputum and stool specimens from children (

References

    1. World Health Organization. Global tuberculosis report 2019. Geneva, Switzerland: WHO, 2019.
    1. Welday SH, Kimang’a AN, Kabera BM, et al. . Stool as appropriate sample for the diagnosis of Mycobacterium tuberculosis by Gene Xpert test. Open J Respir Dis 2014; 4:83.
    1. Banada PP, Naidoo U, Deshpande S, et al. . A novel sample processing method for rapid detection of tuberculosis in the stool of pediatric patients using the Xpert MTB/RIF assay. PLoS One 2016; 11:e0151980.
    1. Khan EA, Starke JR. Diagnosis of tuberculosis in children: increased need for better methods. Emerg Infect Dis 1995; 1:115–23.
    1. Dodd PJ, Gardiner E, Coghlan R, Seddon JA. Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study. Lancet Glob Health 2014; 2:e453–9.
    1. Chipinduro M, Mateveke K, Makamure B, Ferrand RA, Gomo E. Stool Xpert® MTB/RIF test for the diagnosis of childhood pulmonary tuberculosis at primary clinics in Zimbabwe. Int J Tuberc Lung Dis 2017; 21:161–6.
    1. MacLean E, Sulis G, Denkinger CM, Johnston JC, Pai M, Khana FA. Diagnostic accuracy of stool Xpert MTB/RIF for detection of pulmonary tuberculosis in children: a systematic review and meta-analysis. J Clin Microbiol 2019; 57:1–12.
    1. Blakemore R, Story E, Helb D, et al. . Evaluation of the analytical performance of the Xpert MTB/RIF assay. J Clin Microbiol 2010; 48:2495–501.
    1. Atherton RR, Cresswell FV, Ellis J, Kitaka SB, Boulware DR. Xpert MTB/RIF ultra for tuberculosis testing in children: a mini-review and commentary. Front Pediatr 2019; 7:34.
    1. Alland D, Rowneki M, Smith L, et al. . Xpert MTB/RIF Ultra: a new near-patient TB test with sensitivity equal to culture. In: 15th Conference on Retroviruses and Opportunistic Infections, Seattle, WA, 2015:23–6.
    1. Dorman SE, Schumacher SG, Alland D, et al. . Study Team . Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study. Lancet Infect Dis 2018; 18:76–84.
    1. Bahr NC, Nuwagira E, Evans EE, et al. . Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: a prospective cohort study. Lancet Infect Dis 2018; 18:68–75.
    1. World Health Organization. WHO meeting report of a technical expert consultation: non-inferiority analysis of Xpert MTB/RIF Ultra compared to Xpert MTB/RIF. WHO/HTM/TB/2017.04. Geneva, Switzerland: WHO, 2017.
    1. World Health Organization. National guidelines for the management of tuberculosis in children 2nd edition. 2nd ed. Geneva, Switzerland: WHO, 2016.
    1. Rahman SMM, Maliha UT, Ahmed S, et al. . Evaluation of Xpert MTB/RIF assay for detection of Mycobacterium tuberculosis in stool samples of adults with pulmonary tuberculosis. PLoS One 2018; 13:e0203063.
    1. Kent PT, Kubica GP.. Public health mycobacteriology: a guide for the level III laboratory. Atlanta, GA: Centers for Disease Control and Prevention, 1985.
    1. Canetti G, Fox W, Khomenko A, et al. . Advances in techniques of testing mycobacterial drug sensitivity, and the use of sensitivity tests in tuberculosis control programmes. Bull World Health Organ 1969; 41:21–43.
    1. Nicol MP, Workman L, Prins M, et al. . Accuracy of Xpert MTB/RIF Ultra for the diagnosis of pulmonary tuberculosis in children. Pediatr Infect Dis J 2018; 37:e261–3.
    1. Leeflang MMG, Rutjes AWS, Reitsma JB, Hooft L, Bossuyt PMM. Variation of a test’s sensitivity and specificity with disease prevalence. Can Med Assoc J 2013; 185:E537–44.
    1. Leeflang MMG, Bossuyt PMM, Irwig L. Diagnostic test accuracy may vary with prevalence: implications for evidence-based diagnosis. J Clin Epidemiol 2009; 62:5–12.
    1. Mesman AW, Soto M, Coit J, et al. . Correction to: detection of Mycobacterium tuberculosis in pediatric stool samples using TruTip technology. BMC Infect Dis 2019; 19:856.
    1. Nicol MP, Spiers K, Workman L, et al. . Xpert MTB/RIF testing of stool samples for the diagnosis of pulmonary tuberculosis in children. Clin Infect Dis 2013; 57:e18–21.
    1. Drain PK, Bajema KL, Dowdy D, et al. . Incipient and subclinical tuberculosis: a clinical review of early stages and progression of infection. Clin Microbiol Rev 2018; 31:e00021–18.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren