Multicountry assessment of tongue swabs for tuberculosis using a common protocol for Xpert MTB/RIF Ultra testing: a prospective diagnostic accuracy study
23 affiliations
- 1FIND, Geneva, Switzerland
- 2University of California San Francisco - Viet Nam Tuberculosis Program (UCSF-VNTP), Hanoi, Viet Nam; Center for Promotion of Advancement of Society (CPAS), Hanoi, Viet Nam
- 3College of Medicine, De La Salle Medical and Health Sciences Institute, Dasmariñas, Philippines
- 4Zankli Research Center, Bingham University, Karu, Nigeria
- 5Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru
- 6Medical University of South Carolina, Charleston, SC, USA
- 7Frontier Science Foundation, Brookline, MA, USA
- 8Vietnam National Lung Hospital, Hanoi, Viet Nam
- 9Division of Medical Microbiology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Division of Medical Microbiology, National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa
- 10Makerere University Biomedical Research Centre, Kampala, Uganda
- 11Department of Community Medicine, Christian Medical College, Vellore, India
- 12Division of Pulmonary Diseases and Critical Care Medicine, University of California Irvine, Irvine, CA, USA; Center for Tuberculosis, Institute for Global Health Sciences, University of California San Francisco, San Francisco, CA, USA
- 13DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa; Division of Molecular Biology and Human Genetics, SA MRC Centre for Molecular and Cellular Biology, Tygerberg, South Africa
- 14Centre for Infectious Disease Research in Zambia (CIDRZ), Lusaka, Zambia
- 15Division of Medical Microbiology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
- 16College of Health Sciences, Makerere University, Kampala, Uganda
- 17Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru; Department of Epidemiology, School of Public and Population Health, The University of Texas Medical Branch, Galveston, TX, USA
- 18Rutgers University New Jersey Medical School, Newark, NJ, USA
- 19Department of Infectious Disease and Tropical Medicine, Heidelberg University Hospital, Heidelberg, Germany; German Center of Infection Research, partner site Heidelberg, Germany
- 20KNCV Tuberculosis Foundation, Hague, Netherlands
- 21Johns Hopkins University School of Medicine, Baltimore, MD, USA
- 22Center for Tuberculosis, Institute for Global Health Sciences, University of California San Francisco, San Francisco, CA, USA
- 23Division of Pulmonary Diseases and Critical Care Medicine, University of California Irvine, Irvine, CA, USA; Center for Tuberculosis, Institute for Global Health Sciences, University of California San Francisco, San Francisco, CA, USA. Electronic address: [email protected]
Abstract
BACKGROUND: Despite advancements in tuberculosis diagnostics, many cases remain unconfirmed because of challenges in conventional sputum-based testing. This study aimed to evaluate the diagnostic accuracy of tongue swab sampling as a non-invasive alternative for tuberculosis diagnosis using Xpert MTB/RIF Ultra (Ultra). METHODS: We conducted a large-scale, multicountry, prospective diagnostic accuracy study of Ultra using tongue swabs in people with presumptive pulmonary tuberculosis. Participants were enrolled consecutively at primary health centres and hospitals across eight countries from June 26, 2023, to Feb 15, 2024, and the study was coordinated by three consortia. Eligible participants were individuals aged 12 years or older or 18 years or older, according to the consortium involved, with presumptive pulmonary tuberculosis or at least one risk factor for tuberculosis and a positive tuberculosis screening test at the select consortia. Standardised tongue swab collection and processing protocols were used in all countries. Sensitivity and specificity with 95% CI values were calculated against sputum liquid or solid culture (primary) and sputum Ultra (secondary) reference standards using Wilson's score method. Fisher's exact tests were used for subgroup comparisons, with p values < 0·05 considered statistically significant. FINDINGS: Among the 1844 participants included in the analysis, 389 tested positive and 1455 tested negative for pulmonary tuberculosis based on the primary sputum culture reference standard. 871 (47·2%) participants were female and 973 (52·7%) were male, with a mean age of 43 years (range 12-90). Among the 1844 participants, 399 (21·7%) were enrolled in Viet Nam, 166 (9·0%) in India, 427 (23·2%) in South Africa, 271 (14·7%) in the Philippines, 138 (7·5%) in Nigeria, 102 (5·5%) in Zambia, 175 (9·5%) in Uganda, and 166 (9·0%) in Peru. Tongue swab Ultra testing showed a sensitivity of 65·6% (95% CI 60·6-70·3) and specificity of 98·5% (95% CI 97·7-99·1) against the culture-based reference standard. Sensitivity estimates varied across collection centres and were higher in individuals without HIV than in those living with HIV (68·4% vs 50·0%; absolute difference 18·4 percentage points [95% CI 3·3-33·4]). When sputum Ultra was used as the reference standard, sensitivity was 75·4% (95% CI 69·0-78·8). Tongue swab Ultra showed higher sensitivity than sputum smear microscopy. Invalid or error result rates were variable and high at certain sites (range 0-16%). INTERPRETATION: Tongue swabs are a promising sample type for rapid diagnostic tests for tuberculosis, with moderate sensitivity and high specificity when Ultra was used as the reference standard. However, further research is needed to optimise protocols for Ultra testing and develop assays tailored to tongue swab specimens. Adoption of tongue swab-based molecular testing could expand tuberculosis diagnostics access, especially for populations unable to produce sputum, thus supporting global tuberculosis elimination goals. FUNDING: National Institute of Allergy and Infectious Diseases, United States Agency for International Development.
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BibTeX
@article{vos2026multicountry,
title = {{Multicountry assessment of tongue swabs for tuberculosis using a common protocol for Xpert MTB/RIF Ultra testing: a prospective diagnostic accuracy study}},
author = {Margaretha de Vos and Hien Le and Danaida Marcelo and Bukola Ajide and Karla G. Alí-Francia and April Borkman and Rudie Desravines and Hoang Thi Chang and Wentzel Bruce Dowling and Louis Henry Kamulegeya and Sam David Marconi and Caitlin A. Moe and Loren Rockman and Brian Shuma and Devasahayam Jesudas Christopher and Nchimunya Hapeela and Monde Muyoyeta and Lydia Nakiyingi and Grant Theron and Cesar Ugarte-Gil and Nguyen Van Hung and Dinh Van Luong and Charles Yu and David Alland and Claudia Maria Denkinger and Jerrold J. Ellner and Susan E. Dorman and Kristin Kremer and Yukari Carol Manabe and Payam Nahid and Morten Rühwald and M Shah and Adam Penn‐Nicholson and Adithya Cattamanchi and John Bimba and Abigail Abi Daniel and Abubakar Adamu and Agnes Malobela and Alabi Alfa and Amritha Ravikumar and Anathi Ngxakeni and Angelita Pabruada and Ankur Gupta‐Wright and Balamugesh Thangakunam and Bassey Asukwo Ekpenyong and Benard Adean and Bharath Karthikeyan and Bianca Gonçalves Tasca and Camille Felizardo and Camray Botha and Carlos Zamudio and Carolina Moron and Catherine Cook and Charmaine Van der Walt and Cherrie Ann Villarin and Chukwuma Anyaike and Chumani Hatile and Desiree L Mbu and Divya Mangal and Doan Thu Ha},
journal = {The Lancet Microbe},
year = {2026},
month = may,
doi = {10.1016/j.lanmic.2025.101330},
url = {https://doi.org/10.1016/j.lanmic.2025.101330},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Multicountry assessment of tongue swabs for tuberculosis using a common protocol for Xpert MTB/RIF Ultra testing: a prospective diagnostic accuracy study
AU - Margaretha de Vos
AU - Hien Le
AU - Danaida Marcelo
AU - Bukola Ajide
AU - Karla G. Alí-Francia
AU - April Borkman
AU - Rudie Desravines
AU - Hoang Thi Chang
AU - Wentzel Bruce Dowling
AU - Louis Henry Kamulegeya
AU - Sam David Marconi
AU - Caitlin A. Moe
AU - Loren Rockman
AU - Brian Shuma
AU - Devasahayam Jesudas Christopher
AU - Nchimunya Hapeela
AU - Monde Muyoyeta
AU - Lydia Nakiyingi
AU - Grant Theron
AU - Cesar Ugarte-Gil
AU - Nguyen Van Hung
AU - Dinh Van Luong
AU - Charles Yu
AU - David Alland
AU - Claudia Maria Denkinger
AU - Jerrold J. Ellner
AU - Susan E. Dorman
AU - Kristin Kremer
AU - Yukari Carol Manabe
AU - Payam Nahid
AU - Morten Rühwald
AU - M Shah
AU - Adam Penn‐Nicholson
AU - Adithya Cattamanchi
AU - John Bimba
AU - Abigail Abi Daniel
AU - Abubakar Adamu
AU - Agnes Malobela
AU - Alabi Alfa
AU - Amritha Ravikumar
AU - Anathi Ngxakeni
AU - Angelita Pabruada
AU - Ankur Gupta‐Wright
AU - Balamugesh Thangakunam
AU - Bassey Asukwo Ekpenyong
AU - Benard Adean
AU - Bharath Karthikeyan
AU - Bianca Gonçalves Tasca
AU - Camille Felizardo
AU - Camray Botha
AU - Carlos Zamudio
AU - Carolina Moron
AU - Catherine Cook
AU - Charmaine Van der Walt
AU - Cherrie Ann Villarin
AU - Chukwuma Anyaike
AU - Chumani Hatile
AU - Desiree L Mbu
AU - Divya Mangal
AU - Doan Thu Ha
PY - 2026
DA - 2026/05/15
JO - The Lancet Microbe
DO - 10.1016/j.lanmic.2025.101330
UR - https://doi.org/10.1016/j.lanmic.2025.101330
AB - BACKGROUND: Despite advancements in tuberculosis diagnostics, many cases remain unconfirmed because of challenges in conventional sputum-based testing. This study aimed to evaluate the diagnostic accuracy of tongue swab sampling as a non-invasive alternative for tuberculosis diagnosis using Xpert MTB/RIF Ultra (Ultra). METHODS: We conducted a large-scale, multicountry, prospective diagnostic accuracy study of Ultra using tongue swabs in people with presumptive pulmonary tuberculosis. Participants were enrolled consecutively at primary health centres and hospitals across eight countries from June 26, 2023, to Feb 15, 2024, and the study was coordinated by three consortia. Eligible participants were individuals aged 12 years or older or 18 years or older, according to the consortium involved, with presumptive pulmonary tuberculosis or at least one risk factor for tuberculosis and a positive tuberculosis screening test at the select consortia. Standardised tongue swab collection and processing protocols were used in all countries. Sensitivity and specificity with 95% CI values were calculated against sputum liquid or solid culture (primary) and sputum Ultra (secondary) reference standards using Wilson's score method. Fisher's exact tests were used for subgroup comparisons, with p values < 0·05 considered statistically significant. FINDINGS: Among the 1844 participants included in the analysis, 389 tested positive and 1455 tested negative for pulmonary tuberculosis based on the primary sputum culture reference standard. 871 (47·2%) participants were female and 973 (52·7%) were male, with a mean age of 43 years (range 12-90). Among the 1844 participants, 399 (21·7%) were enrolled in Viet Nam, 166 (9·0%) in India, 427 (23·2%) in South Africa, 271 (14·7%) in the Philippines, 138 (7·5%) in Nigeria, 102 (5·5%) in Zambia, 175 (9·5%) in Uganda, and 166 (9·0%) in Peru. Tongue swab Ultra testing showed a sensitivity of 65·6% (95% CI 60·6-70·3) and specificity of 98·5% (95% CI 97·7-99·1) against the culture-based reference standard. Sensitivity estimates varied across collection centres and were higher in individuals without HIV than in those living with HIV (68·4% vs 50·0%; absolute difference 18·4 percentage points [95% CI 3·3-33·4]). When sputum Ultra was used as the reference standard, sensitivity was 75·4% (95% CI 69·0-78·8). Tongue swab Ultra showed higher sensitivity than sputum smear microscopy. Invalid or error result rates were variable and high at certain sites (range 0-16%). INTERPRETATION: Tongue swabs are a promising sample type for rapid diagnostic tests for tuberculosis, with moderate sensitivity and high specificity when Ultra was used as the reference standard. However, further research is needed to optimise protocols for Ultra testing and develop assays tailored to tongue swab specimens. Adoption of tongue swab-based molecular testing could expand tuberculosis diagnostics access, especially for populations unable to produce sputum, thus supporting global tuberculosis elimination goals. FUNDING: National Institute of Allergy and Infectious Diseases, United States Agency for International Development.
SN - 2666-5247
ER -