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Accuracy of Xpert Ultra for the diagnosis of paediatric tuberculosis in a low TB burden country: a prospective multicentre study
  1. David Aguilera-Alonso1,2,3,4,
  2. Gonzalo Solís-García5,
  3. Antoni Noguera-Julian3,6,7,8,9,
  4. Julián González-Martín4,10,
  5. Angely Román Cobeña10,
  6. Fernando Baquero-Artigao3,4,11,
  7. Carlos Toro Rueda12,
  8. Paula Rodríguez-Molino3,4,11,
  9. Iván Bloise Sánchez12,
  10. Teresa Vallmanya13,
  11. Albert Bernet-Sánchez14,
  12. Laura Minguell Domingo13,
  13. Adriana Rubio13,
  14. Jesús Saavedra-Lozano1,2,3,4,15,
  15. María Jesús Ruiz-Serrano16,
  16. Daniel Blázquez-Gamero3,15,17,18,
  17. Paula López-Roa19,
  18. David Gomez-Pastrana20,
  19. María Dolores López Prieto21,
  20. Eva María López Medina22,
  21. Ana Gil-Brusola23,
  22. Andrea Martín Nalda24,
  23. Antonio Soriano-Arandes24,
  24. Teresa Tórtola25,26,
  25. Lola Falcon-Neyra27,28,
  26. Verónica González Galán29,
  27. Marc Tebruegge30,31,
  28. Begoña Santiago-García1,2,3,4
  1. 1Paediatric Infectious Diseases Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain
  2. 2Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
  3. 3Translational Research Network in Paediatric Infectious Diseases (RITIP), Madrid, Spain
  4. 4Centro de Investigación Biomedica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
  5. 5Neonatology Department, The Hospital for Sick Children, Toronto, Ontario, Canada
  6. 6Malalties Infeccioses i Resposta Inflamatòria Sistèmica en Pediatria, Unitat d'Infeccions, Servei de Pediatria, Hospital Sant Joan de Deu, Barcelona, Spain
  7. 7Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona, Spain
  8. 8Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
  9. 9Department of Paediatrics, University of Barcelona, Barcelona, Spain
  10. 10Servei de Microbiologia, Hospital Clinic de Barcelona, Barcelona, Spain
  11. 11Department of Paediatrics, Infectious, and Tropical Diseases, Hospital La Paz, Madrid, Spain
  12. 12Department of Microbiology, Hospital La Paz, Madrid, Spain
  13. 13Department of Paediatrics, Hospital Universitari Arnau de Vilanova, Lleida, Spain
  14. 14Laboratory of Microbiology, Hospital Universitari Arnau de Vilanova, Lleida, Spain
  15. 15Universidad Complutense, Madrid, Spain
  16. 16Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
  17. 17Paediatric Infectious Diseases Unit, Hospital Universitario 12 de Octubre, Madrid, Spain
  18. 18Instituto de Investigación Hospital 12 de Octubre (imas12), Madrid, Spain
  19. 19Department of Microbiology, Hospital Universitario 12 de Octubre, Madrid, Spain
  20. 20Paediatric Respiratory Unit, Hospital Universitario Materno-Infantil de Jerez, Jerez de la Frontera, Spain
  21. 21Unit of Infectious Diseases and Clinical Microbiology, Hospital Universitario de Jerez de la Frontera, Jerez de la Frontera, Spain
  22. 22Department of Paediatrics, Consorci Hospital General Universitari de Valencia, Valencia, Spain
  23. 23Microbiology Department, Hospital La Fe, Valencia, Spain
  24. 24Paediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Vall d'Hebron, Barcelona, Spain
  25. 25Unitat de Micobactèries, Laboratori Supranacional de Referència de l'OMS per a la Tuberculosis, Hospital Vall d'Hebron, Barcelona, Spain
  26. 26PROSICS, Institut Català de la Salut, Barcelona, Spain
  27. 27Department of Infectious Diseases, Rheumatology and Immunodeficiency, Hospital Universitario Virgen del Rocío, Sevilla, Spain
  28. 28Instituto de Investigación Biomédica de Sevilla (IBiS), Sevilla, Spain
  29. 29Clinical Microbiology, Infectious Diseases and Preventive Medicine Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain
  30. 30Department of Paediatrics, Faculty of Medicine, The University of Melbourne, Parkville, Victoria, Australia
  31. 31Department of Infection, Immunity and Inflammation, Great Ormond Street Institute of Child Health, University College London, London, UK
  1. Correspondence to Dr David Aguilera-Alonso, Department of Paediatrics, Hospital General Universitario Gregorio Marañón, Madrid, 28009, Spain; david.aguilera{at}


Introduction Childhood pulmonary tuberculosis (TB) remains a diagnostic challenge. This study aimed to evaluate the performance of Xpert Ultra for the diagnosis of pulmonary TB in children in a low TB prevalence setting.

Methods Prospective, multicentre, diagnostic accuracy study. Children with clinical or radiological suspicion of pulmonary TB were recruited at 11 paediatric units in Spain. Up to three gastric or sputum specimens were taken on 3 consecutive days, and analysed by Xpert MTB/RIF, Xpert Ultra and culture in parallel.

Results 86 children were included (median age 4.9 years, IQR 2.0–10.0; 51.2% male). The final diagnosis was pulmonary TB in 75 patients (87.2%); 33 (44.0%) were microbiologically confirmed. A total of 219 specimens, comprising gastric aspirates (n=194; 88.6%) and sputum specimens (n=25; 11.4%), were analysed. Using culture as reference standard and comparing individual specimens, the sensitivity was 37.8% (14/37) for Xpert MTB/RIF and 81.1% (30/37) for Xpert Ultra (p<0.001); specificity was 98.4% (179/182) and 93.4% (170/182), respectively (p=0.02). In the per-patient analysis, considering positive results on any specimen, the sensitivity was 42.9% (9/21) for Xpert MTB/RIF and 81.0% for Xpert Ultra (17/21, p=0.01); specificity was 96.9% (63/65) and 87.7% (57/65, p=0.07), respectively.

Conclusions In children with pulmonary TB in a low burden setting, Xpert Ultra has significantly higher sensitivity than the previous generation of Xpert assay and only marginally lower specificity. Therefore, in children undergoing evaluation for suspected pulmonary TB, Xpert Ultra should be used in preference to Xpert MTB/RIF whenever possible.

  • Tuberculosis
  • Paediatric Lung Disaese
  • Respiratory Infection

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • DA-A and GS-G are joint first authors.

  • MT and BS-G are joint senior authors.

  • Twitter @DavidAguileraAl, @tonisoriano66

  • Contributors BS-G and MT conceived of the study. BS-G, MT, DA-A, and JS-L designed the study. GS-G, DA-A and BS-G cleaned and analysed the data, and constructed the figures and tables. DA-A, GS-G, BS-G, JS-L and MT wrote the first draft of the manuscript. BS-G and DA-A are responsible for the overall content as guarantors. All authors contributed data to the study, contributed to the data interpretation, critically reviewed the manuscript and approved the final manuscript for submission. MT and BS-G are joint last authors.

  • Funding This study did not receive any project-specific funding. DA-A was supported by the Spanish Ministry of Health – Instituto de Salud Carlos III (ISCIII) and cofunded by the European Union (FEDER) (Contrato Río Hortega CM18/00100). AN-J was supported by 'Subvencions per a la Intensificació de Facultatius Especialistes' (Departament de Salut de la Generalitat de Catalunya, Programa PERIS 2016-2020) (SLT008/18/00193). DBG was supported by the Spanish Ministry of Science and Innovation – Instituto de Salud Carlos III and Fondos FEDER by 'Contratos para la intensificación de la actividad investigadora en el Sistema Nacional de Salud, 2020 (INT20/00086)'. BS-G was supported by the Spanish Ministry of Health – Instituto de Salud Carlos III (ISCIII) and cofunded by the European Union (FEDER) (Contrato Juan Rodés JR16/00036). Xpert cartridges were kindly provided by Cepheid, Sunnyvale, CA, USA.

  • Competing interests MT has received support for conference attendance from Cepheid in the past. The remaining authors declare that they have no potential conflicts of interest.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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