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[Preprint]. 2024 Dec 18:2024.12.17.24317956.

doi: 10.1101/2024.12.17.24317956.

Stool processing methods for Xpert Ultra testing in childhood tuberculosis: A prospective, multi-country accuracy study

Devan Jaganath^{1

2}, Pamela Nabeta³, Mark P Nicol⁴, Robert Castro^{2

5}, Peter Wambi⁶, Heather J Zar⁷, Lesley Workman⁷, Rakesh Lodha⁸, Urvashi B Singh^{8

9}, Ashish Bavdekar¹⁰, Sonali Sanghavi¹¹, André Trollip³, Aurélien Mace³, Maryline Bonnet¹², Manon Lounnas¹³, Petra de Haas¹⁴, Edine Tiemersma¹⁴, David Alland¹⁵, Padmapriya Banada¹⁵, Adithya Cattamanchi^{2

16}, Morten Ruhwald³, Eric Wobudeya⁶, Claudia M Denkinger^{3

17}

Affiliations

¹ Division of Pediatric Infectious Diseases, University of California, San Francisco, San Francisco, USA.
² Center for Tuberculosis, University of California, San Francisco, San Francisco, USA.
³ FIND, Geneva, Switzerland.
⁴ Marshall Centre, School of Biomedical Sciences, University of Western Australia, Perth, Australia.
⁵ Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, USA.
⁶ Walimu, Kampala, Uganda.
⁷ Department of Paedatrics and Child Health, University of Cape Town, Cape Town, South Africa.
⁸ Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
⁹ Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India.
¹⁰ Department of Pediatrics, KEM Hospital, Pune, India.
¹¹ Department of Microbiology, KEM Hospital, Pune, India.
¹² TransVIHMH, University of Montpellier, IRD, Inserm, Montpellier, France.
¹³ University of Montpellier, IRD, CNRS, MIVEGEC, Montpellier, France.
¹⁴ KNCV Tuberculosis Foundation, The Hague, The Netherlands.
¹⁵ Public Health Research Institute, Department of Medicine, Rutgers-New Jersey Medical School, Newark, USA.
¹⁶ Division of Pulmonary Diseases and Critical Care Medicine, University of California Irvine, Orange, USA.
¹⁷ Department of Infectious Disease and Tropical Medicine, University Hospital Heidelberg, German Center of Infection Research, partner site Heidelberg, Germany.

PMID: 39763536
PMCID: PMC11702738
DOI: 10.1101/2024.12.17.24317956

Stool processing methods for Xpert Ultra testing in childhood tuberculosis: A prospective, multi-country accuracy study

Devan Jaganath et al. medRxiv. 2024.

[Preprint]. 2024 Dec 18:2024.12.17.24317956.

doi: 10.1101/2024.12.17.24317956.

Authors

Affiliations

¹ Division of Pediatric Infectious Diseases, University of California, San Francisco, San Francisco, USA.
² Center for Tuberculosis, University of California, San Francisco, San Francisco, USA.
³ FIND, Geneva, Switzerland.
⁴ Marshall Centre, School of Biomedical Sciences, University of Western Australia, Perth, Australia.
⁵ Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, USA.
⁶ Walimu, Kampala, Uganda.
⁷ Department of Paedatrics and Child Health, University of Cape Town, Cape Town, South Africa.
⁸ Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
⁹ Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India.
¹⁰ Department of Pediatrics, KEM Hospital, Pune, India.
¹¹ Department of Microbiology, KEM Hospital, Pune, India.
¹² TransVIHMH, University of Montpellier, IRD, Inserm, Montpellier, France.
¹³ University of Montpellier, IRD, CNRS, MIVEGEC, Montpellier, France.
¹⁴ KNCV Tuberculosis Foundation, The Hague, The Netherlands.
¹⁵ Public Health Research Institute, Department of Medicine, Rutgers-New Jersey Medical School, Newark, USA.
¹⁶ Division of Pulmonary Diseases and Critical Care Medicine, University of California Irvine, Orange, USA.
¹⁷ Department of Infectious Disease and Tropical Medicine, University Hospital Heidelberg, German Center of Infection Research, partner site Heidelberg, Germany.

PMID: 39763536
PMCID: PMC11702738
DOI: 10.1101/2024.12.17.24317956

Update in

Stool processing methods for Xpert Ultra testing in childhood tuberculosis: A prospective, multi-country accuracy study.
Jaganath D, Nabeta P, Nicol MP, Castro R, Wambi P, Zar HJ, Workman L, Lodha R, Singh UB, Bavdekar A, Sanghavi S, Trollip A, Mace A, Bonnet M, Lounnas M, de Haas P, Tiemersma E, Alland D, Banada P, Cattamanchi A, Ruhwald M, Wobudeya E, Denkinger CM; Stool H2H Study Team. Jaganath D, et al. Clin Infect Dis. 2025 Jun 3:ciaf289. doi: 10.1093/cid/ciaf289. Online ahead of print. Clin Infect Dis. 2025. PMID: 40460214

Abstract

Background: Centrifuge-free processing methods support stool Xpert Ultra testing for childhood tuberculosis (TB), but there are limited data on their accuracy, acceptability and usability.

Methods: We conducted a prospective evaluation of stool Xpert Ultra in India, South Africa, and Uganda with three methods: Stool Processing Kit (SPK), Simple One-Step (SOS), and Optimized Sucrose Flotation (OSF). Children <15 years old with presumptive TB had respiratory specimen testing with Xpert Ultra and culture. Stool was tested using Xpert Ultra after processing with each method. We compared the accuracy of each method to a microbiological reference standard (MRS) and a composite reference standard (CRS). We surveyed the laboratory staff to assess acceptability and usability of the methods.

Results: We included 607 children, of whom the median age was 3.5 years (IQR 1.3-7), 48% were female, and 15.5% were HIV positive. Against the MRS, the sensitivities of SPK, SOS and OSF were 36.9% (95% CI 28.6-45.8), 38.6% (95% CI 17.2-51), and 31.3% (95% CI 20.2-44.1), respectively. The specificities of SPK, SOS and OSF were 98.2% (95% CI 96.4-99.3), 97.3% (95% CI 93.7-99.1) and 97.1% (95% CI 93.3-99), respectively. Laboratory staff reported that the methods were acceptable and usable, but SOS was most feasible to implement in a peripheral facility. Sensitivity increased among children who were culture-positive (55-77.3%) and was low (13-16.7%) against the CRS.

Conclusions: Stool processing methods for Xpert Ultra were acceptable, usable, and performed similarly, with highest sensitivity among children with culture-positive TB.

Keywords: Xpert Ultra; centrifuge-free; child; diagnostics; stool; tuberculosis.

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Conflict of interest statement

For potential conflicts of interest, MPN, DA, PB and FIND were involved in the development of SPK, PD and ET for SOS, and MB and ML for OSF. DA holds patents related to tuberculosis detection and drug treatment, and receives royalty payments for one or more of these patents that have been licensed by Rutgers University to Cepheid. The other authors declare no conflicts of interest.

Figures

**Figure 2.. Usability of stool-based Xpert Ultra testing with centrifuge-free processing methods**

See this image and copyright information in PMC

References

1. World Health Organization. WHO consolidated guidelines on tuberculosis. Module 3: diagnosis – rapid diagnostics for tuberculosis detection, third edition. Geneva: World Health Organization, 2024.
1. Moore BK, Graham SM, Nandakumar S, Doyle J, Maloney SA. Pediatric Tuberculosis: A Review of Evidence-Based Best Practices for Clinicians and Health Care Providers. Pathogens 2024; 13(6): 467. - PMC - PubMed
1. Agarwal A, Mathur SB. Stool CBNAAT: Alternative tool in the diagnosis of pulmonary tuberculosis in children. Indian Journal of Tuberculosis 2023. - PubMed
1. Walters E, Gie RP, Hesseling AC, Friedrich SO, Diacon AH, Gie RP. Rapid diagnosis of pediatric intrathoracic tuberculosis from stool samples using the Xpert MTB/RIF Assay: a pilot study. Pediatric Infectious Disease Journal 2012; 31(12): 1316. - PubMed
1. Babo Y, Seremolo B, Bogale M, et al. Comparison of Xpert MTB/RIF Ultra Results of Stool and Sputum in Children with Presumptive Tuberculosis in Southern Ethiopia. Trop 2023; 8(7): 30. - PMC - PubMed

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This is a preprint.

Stool processing methods for Xpert Ultra testing in childhood tuberculosis: A prospective, multi-country accuracy study

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Stool processing methods for Xpert Ultra testing in childhood tuberculosis: A prospective, multi-country accuracy study

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Update in

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Conflict of interest statement

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