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Xpert MTB/RIF diagnosis of childhood tuberculosis from sputum and stool samples in a high TB-HIV-prevalent setting

  • Patrick Orikiriza
  • Margaret Nansumba
  • Dan Nyehangane
  • Mathieu Bastard
  • Ivan Taremwa Mugisha
  • Denis Nansera
  • Juliet Mwanga-Amumpaire
  • Yap BoumII
  • Elias Kumbakumba
  • Maryline Bonnet
Original Article

Abstract

The Xpert MTB/RIF assay is a major advance for diagnosis of tuberculosis (TB) in high-burden countries but is limited in children by their difficulty to produce sputum. We investigated TB in sputum and stool from children with the aim of improving paediatric TB diagnosis. A prospective cohort of children with presumptive TB, provided two sputum or induced sputum at enrolment in a regional referral hospital in Uganda. Stool was collected from those started on TB treatment. All specimen were tested for Xpert MTB/RIF, mycobacteria growth indicator tube (MGIT), Lowenstein Jensen cultures and microscopy (except stool). We compared TB detection between age categories and assessed the performance of Xpert MTB/RIF in sputum and stool. Of the 392 children enrolled, 357 (91.1%) produced at least one sputum sample. Sputum culture yield was 13/357 (3.6%): 3/109 (2.6%), 3/89 (3.2%), 3/101 (2.6%) and 4/44 (8.2%) among children of < 2, 2–5, ≥ 5–10 and > 10 years, respectively (p = 0.599). Xpert MTB/RIF yield was 14/350 (4.0%): 3/104 (2.9%), 4/92 (4.3%), 3/88 (2.9%) and 4/50 (.0%), respectively (p = 0.283). Sensitivity and specificity of Xpert MTB/RIF in sputum against sputum culture were 90.9% (95% CI 58.7–99.8) and 99.1% (99.1–99.8). In stool, it was 55.6% (21.2–86.3) and 98.2% (98.2–100) against Xpert MTB/RIF and culture in sputum. Only a minority of children had microbiologically confirmed TB with a higher proportion in children above 10 years. Although sensitivity of Xpert MTB/RIF in stool was low, with good optimization, it might be a good alternative to sputum in children.

Keywords

Childhood tuberculosis Stool Sputum Xpert MTB/RIF 

Notes

Acknowledgments

We express our gratitude to the study participants. We also thank the nurses and laboratory personnel of Epicentre that participated in data collection. Special thanks to Dr. Pierre de Beaudrap (IRD, UMR196-CEPED, France) for his priceless contribution in the design of this study. We appreciate Mbarara University and hospital colleagues, especially late Pr. Julius Kiwanuka who supported the study through constructive advice and patient referral to the study. We also thank the members of our scientific committee for their support: Pr. Ben Marais (Sydney Institute for Emerging Infectious Diseases, Australia), Dr. Francis Varaine (Médecins Sans Frontières, France), Dr. Andrew Ramsay (TDR/OMS, Switzerland and University of St Andrews, UK) and Dr. Philippe Msellati (IRD UMI 233 TransVIHMI–UM–INSERM U1175, France).

Funding

This study was funded by Médecins Sans Frontières.

Compliance with ethical standards

All authors contributed sufficiently to the scientific work and therefore share collective responsibility and accountability for the results. Consent to submit this work has been received explicitly from all co-authors.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Approvals were received from Mbarara University Research Ethics Committee, the Uganda National Council for Science and Technology and The Comité de Protection des Personnes of Ile de France XI, Saint-Germain, Laye, France.

Informed consent

Informed consent was obtained from all individual participants included in this study. Particularly, written informed consent was given by the parent or legal guardian and assent by children of 7 years or older.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Patrick Orikiriza
    • 1
    • 2
  • Margaret Nansumba
    • 1
  • Dan Nyehangane
    • 1
  • Mathieu Bastard
    • 3
  • Ivan Taremwa Mugisha
    • 1
  • Denis Nansera
    • 4
  • Juliet Mwanga-Amumpaire
    • 1
    • 4
  • Yap BoumII
    • 1
    • 4
  • Elias Kumbakumba
    • 4
  • Maryline Bonnet
    • 1
    • 2
    • 5
  1. 1.Epicentre Mbarara Research CentreMbararaUganda
  2. 2.Université de MontpellierMontpellierFrance
  3. 3.EpicentreParisFrance
  4. 4.Mbarara University of Science and TechnologyMbararaUganda
  5. 5.IRD UMI233/ INSERM U1175MontpellierFrance

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