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Volume 31, Number 3—March 2025
Online Report

Lessons Learned from Early Implementation and Scale-up of Stool-Based Xpert Testing to Diagnose Tuberculosis in Children

Eveline Klinkenberg1Comments to Author , Petra de Haas1, Charles Manyonge, Joanita Namutebi, Bibiche Mujangi, Hebert Mutunzi, Amri Kingalu, Nkiru Nwokoye, Kuzani Mbendera, Yohannes D. Babo, Gulmira Kalmambetova, Gunta Dravniece, Winnie Mwanza, Ahmed Bedru, Degu D. Jerene, Lisa V. Adams, Andwele Mwansasu, and Charlotte Colvin
Author affiliation: ConnectTB, the Hague, the Netherlands (E. Klinkenberg); Amsterdam University Medical Centers, Amsterdam, the Netherlands (E. Klinkenberg); KNCV Tuberculosis Foundation, the Hague (P. de Haas, D. D. Jerene); Supra National Reference Laboratory, Kampala, Uganda (C. Manyonge, J. Namutebi); National Reference Laboratory and National TB Program, Kinshasa, Democratic Republic of Congo (B. Mujangi); USAID, Infectious Disease Detection and Surveillance Project, Harare, Zimbabwe (H. Mutunzi); Central Tuberculosis Reference Laboratory, Dar es Salaam, Tanzania (A. Kingalu); KNCV Nigeria, Abuja, Nigeria (N. Nwokoye); National Tuberculosis Program, Lilongwe, Malawi (K. Mbendera); KNCV Tuberculosis Foundation, Addis Ababa, Ethiopia (Y.D. Babo, A. Bedru); Ministry of Health, Bishek, Kyrgyzstan (G. Kalmambetova); PATH, Kiev, Ukraine (G. Dravniece); Ministry of Health, Lusaka, Zambia (W. Mwanza); Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA (L.V. Adams); USAID Infectious Disease Detection and Surveillance Project, Washington, DC, USA (A. Mwansasu); USAID Bureau for Global Health, Washington (C. Colvin); Credence Management Solutions, LLC, McLean, Virginia, USA (C. Colvin)

Main Article

Table 2

Summary of stool testing data from 9 early adopter countries who presented during the TB Union World Lung Health Conference Workshop on stool-based Xpert testing, 2023*

Country Phase No. facilities or regions† Period for which data are included Period, mo No. children
 MTBC yield in stool Average no. children tested/mo
Tested (with valid results) With MTBC in stool With RR MTBC
Malawi (11)‡ Pilot 8 facilities Nov 22–May 23 7 536 (503) 31 2 6.2 83
DRC§ Pilot 25 facilities Jul 22–Nov 22 5 793 (775) 134 3 17.3 59
Kyrgyzstan§ Pilot 1 region April 22–Dec 22 9 245 (241) 19 1 7.9 27
Ukraine (12)§ Pilot 12 regions Nov 21–Sept 22 11 168 (162) 18 3 11.1 15
Ethiopia§ Pilot 31 facilities Oct 20–Dec 21 14 371 (368) 24 0 6.5 27
Ethiopia§ Routine 45 facilities Jun 23–Oct 23 5 1,035¶ 22 1 2.1 207
Zimbabwe§ Routine 42 facilities# Jan–Sept 23 9 912 (878) 12 1 1.4 101
Zambia (13)‡ Routine Nationwide Jan 21–Jun 22 18 14,884¶ 157 5 1.1 827
Tanzania§ Routine 113 facilities April 23–Oct 23 7 696 (609) 35 1 5.7 99
Nigeria (16)§
 Routine
 14 regions**
 Oct 20–Sept 23
 36
 52,117 (50,774)
 2,440
 26
 4.8
 1,410
Overall Oct 20–Sept 23 121 71,757 (70,229) 2,892 43 4.1†† 582

*DRC, Democratic Republic of Congo; MTBC, mycobacterium tuberculosis complex; RIF, rifampicin; TB, tuberculosis. †For several countries the data have been published or are submitted for publication since they were presented at the union workshop as per references included below. ‡Mixture of Xpert MTB/RIF and Xpert Ultra (both Cepheid, https://www.cepheid.com) used, depending on availability at the facility. §Xpert Ultra used. ¶No differentiation in total children tested and those with valid results available region means all TB diagnostic sites in a region perform stool, otherwise number of implementing facilities is indicated; region may have different names in different countries (i.e., state in Nigeria, oblast in Kyrgyzstan and Ukraine). #In 8/10 provinces. **Data presented were from 14 regions, although Nigeria is since 2021 implementing stool-based testing in all 36 states (regions). ††Weighted average.

Main Article

References
  1. World Health Organization. Global tuberculosis report 2023. Geneva: The Organization; 2023.
  2. World Health Organization. Roadmap towards ending TB in children and adolescents, third edition. Geneva: The Organization; 2023.
  3. World Health Organization. Molecular assays intended as initial tests for the diagnosis of pulmonary and extrapulmonary TB and rifampicin resistance in adults and children: rapid communication. Policy update. Geneva: The Organization; 2020.
  4. World Health Organization. WHO operational handbook on tuberculosis. Module 3: diagnosis—rapid diagnostics for tuberculosis detection. Geneva: The Organization; 2020.
  5. World Health Organization. Consolidated guidelines on tuberculosis. Module 5: management of tuberculosis in children and adolescents. Geneva: The Organization; 2022.
  6. Mafirakureva  N, Klinkenberg  E, Spruijt  I, Levy  J, Shaweno  D, de Haas  P, et al. Xpert Ultra stool testing to diagnose tuberculosis in children in Ethiopia and Indonesia: a model-based cost-effectiveness analysis. BMJ Open. 2022;12:e058388. DOIPubMedGoogle Scholar
  7. World Health Organization Global Laboratory Initiative. Practical manual of processing stool samples for diagnosis of childhood TB. Geneva: The Organization; 2022.
  8. de Haas  P, Yenew  B, Mengesha  E, Slyzkyi  A, Gashu  Z, Lounnas  M, et al. The Simple One-Step (SOS) stool processing method for use with the Xpert MTB/RIF assay for a child-friendly diagnosis of tuberculosis closer to the point of care. J Clin Microbiol. 2021;59:e0040621. DOIPubMedGoogle Scholar
  9. Jasumback  CL, Dlamini  Q, Kahari  J, Maphalala  G, Dlamini  MG, Dube  GS, et al. Laboratory comparison of stool processing methods for Xpert® Ultra. Public Health Action. 2021;11:55–7. DOIPubMedGoogle Scholar
  10. KNCV. The SOS Stoolbox: an implementation package for the SOS stool method to detect TB and rifampicin resistance [cited 2023 Dec 15]. https://www.kncvtbc.org/en/sos-stoolbox
  11. Mpunga  J, Mbendera  K, Mwenyenkulu  T, Kanyerere  H, Girma  B, Chirwa  S, et al. Feasibility of stool-based Xpert for the diagnosis of childhood pulmonary tuberculosis in Malawi. IJTLD Open. 2025. In press.
  12. Diuzheva  O, Skoklyuk  L, Zherebko  N, Barbova  A, Germanovych  M, Klinkenberg  E, et al. Paving the way to innovative, child-friendly pediatric diagnostic methods for tuberculosis: introduction of stool-based testing in Ukraine. Trop Med Infect Dis. 2024;9:209. DOIPubMedGoogle Scholar
  13. Nwokoye  N, Odume  B, Nwadike  P, Anaedobe  I, Mangoro  Z, Umoren  M, et al. Impact of the stool-based Xpert test on childhood tuberculosis diagnosis in selected states in Nigeria. Trop Med Infect Dis. 2024;9:100. DOIPubMedGoogle Scholar
  14. Mwanza  W, Lutinala  M, Mundia  K, Klinkenberg  E, de Haas  P, Kabaso  M, et al. Stool-based Xpert testing for diagnosis of TB in children and critically ill adults. Int J Tuberc Lung Dis. 2025;29:75–9. DOIPubMedGoogle Scholar
  15. Albert  H, Rupani  S, Masini  E, Ogoro  J, Kamene  M, Geocaniga-Gaviola  D, et al. Optimizing diagnostic networks to increase patient access to TB diagnostic services: Development of the diagnostic network optimization (DNO) approach and learnings from its application in Kenya, India and the Philippines. PLoS One. 2023;18:e0279677. DOIPubMedGoogle Scholar
  16. Kao  K, Kohli  M, Gautam  J, Kassa  H, Acellam  S, Ndungu  J, et al. Strengthening health systems through essential diagnostic lists and diagnostic network optimization. PLOS Glob Public Health. 2023;3:e0001773. DOIPubMedGoogle Scholar
  17. Yenew  B, de Haas  P, Diriba  G, Kebede  A, Sherefdin  B, Demissie  Y, et al. Optimization of the Simple One-Step stool processing method to diagnose tuberculosis: evaluation of robustness and stool transport conditions for global implementation. Microbiol Spectr. 2023;11:e0117123. DOIPubMedGoogle Scholar
  18. de Haas  P, Nhung  NV, Hng  NT, Hoà  NB, Loan  NB, Thanh  NTK, et al. Introduction of the Simple One-Step stool Xpert Ultra method to detect TB in children and adults. Int J Tuberc Lung Dis. 2023;27:19–27. DOIPubMedGoogle Scholar
  19. Gidado  M, Nwokoye  N, Nwadike  P, Ajiboye  P, Eneogu  R, Useni  S, et al. Unsuccessful Xpert® MTB/RIF results: the Nigerian experience. Public Health Action. 2018;8:2–6. DOIPubMedGoogle Scholar
  20. Rahman  SMM, Maliha  UT, Ahmed  S, Kabir  S, Khatun  R, Shah  JA, 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. DOIPubMedGoogle Scholar
  21. Sultana  S, Ansar  A, Saif-Ur-Rahman  KM. Stool specimen for diagnosis of pulmonary tuberculosis in adults: protocol for a systematic review and meta-analysis. BMJ Open. 2021;11:e052212. DOIPubMedGoogle Scholar
  22. Yu  X, Wang  F, Ren  R, Dong  L, Xue  Y, Zhao  L, et al. Xpert MTB/RIF Ultra assay using stool: an effective solution for bacilli identification from adult pulmonary tuberculosis suspects without expectorated sputum. Microbiol Spectr. 2023;11:e0126523. DOIPubMedGoogle Scholar
  23. Chibolela  M, de Haas  P, Klinkenberg  E, Kosloff  B, Chunda-Liyoka  C, Lungu  P, et al. Use of stool swabs in molecular transport media increases access to Xpert Ultra testing for TB in children. Int J Tuberc Lung Dis. 2023;27:612–8. DOIPubMedGoogle Scholar
  24. Ngangue  YR, Mbuli  C, Neh  A, Nshom  E, Koudjou  A, Palmer  D, et al. Diagnostic accuracy of the Truenat MTB Plus assay and comparison with the Xpert MTB/RIF assay to detect tuberculosis among hospital outpatients in Cameroon. J Clin Microbiol. 2022;60:e0015522. DOIPubMedGoogle Scholar
  25. Penn-Nicholson  A, Gomathi  SN, Ugarte-Gil  C, Meaza  A, Lavu  E, Patel  P, et al.; Truenat Trial Consortium; Members of the Truenat Trial Consortium. A prospective multicentre diagnostic accuracy study for the Truenat tuberculosis assays. Eur Respir J. 2021;58:2100526. DOIPubMedGoogle Scholar
  26. Banada  PP, Naidoo  U, Deshpande  S, Karim  F, Flynn  JL, O’Malley  M, 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. DOIPubMedGoogle Scholar
  27. MacLean  E, Sulis  G, Denkinger  CM, Johnston  JC, Pai  M, Ahmad Khan  F. 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:e02057–18. DOIPubMedGoogle Scholar
  28. Mesman  AW, Rodriguez  C, Ager  E, Coit  J, Trevisi  L, Franke  MF. Diagnostic accuracy of molecular detection of Mycobacterium tuberculosis in pediatric stool samples: A systematic review and meta-analysis. Tuberculosis (Edinb). 2019;119:101878. DOIPubMedGoogle Scholar
  29. Mesman  AW, Soto  M, Coit  J, Calderon  R, Aliaga  J, Pollock  NR, et al. Correction to: Detection of Mycobacterium tuberculosis in pediatric stool samples using TruTip technology. BMC Infect Dis. 2019;19:856. DOIPubMedGoogle Scholar

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1These first authors contributed equally to this article.

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