Diagnostic yield of tongue swab- compared to sputum-based molecular testing for tuberculosis in four high-burden countries

BackgroundTongue swabs are a promising alternative specimen for tuberculosis (TB) diagnosis, with high specificity (>98%) but lower sensitivity than sputum-based molecular tests. We investigated whether increased sample availability could offset lower sensitivity, resulting in similar diagnostic yield. MethodsFrom September 2024-January 2025, we screened consecutive people with presumptive TB at health centers in the Philippines, Vietnam, Uganda, and Zambia. Enrolled participants were asked to provide tongue swabs and referred for routine sputum collection. Tongue swabs were tested in research laboratories using the MiniDock MTB Test (Guangzhou Pluslife Biotech Co., Ltd., China); sputum was tested using WHO-recommended molecular testing per national guidelines. We compared diagnostic yield, defined as positive test results among those seeking testing, between tongue swab- and sputum-based molecular testing with a pre-specified non-inferiority margin of {+/-}3%. FindingsOf 1,639 participants, 851 (51{middle dot}9%) were female, 415 (25{middle dot}3%) were living with HIV and 132 (8{middle dot}1%) were children <5 years. Overall, 1,389 (84{middle dot}7%) provided sputum, while 1,637 (99{middle dot}9%) provided tongue swabs. Diagnostic yield was similar for tongue swab-(63/1639, 3{middle dot}8%) and sputum-based (68/1639, 4{middle dot}1%) molecular testing, and within the pre-specified non-inferiority margin (difference -0{middle dot}3%, 95%CI -1{middle dot}2 to +0{middle dot}6). Results were consistent across subgroups by country, age, sex, and HIV status. InterpretationTB diagnostic yield from tongue swabs was non-inferior to sputum-based molecular testing. These data support scale-up of swab- based molecular platforms as a lower-cost alternative to sputum-based tests, particularly in settings where sputum collection is challenging, or smear microscopy remains standard. FundingSupported by the Bill and Melinda Gates Foundation. RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSO_LITongue swabs are a promising alternative specimen type for tuberculosis (TB) diagnosis. C_LIO_LIStudies have demonstrated high specificity (>98%) but lower sensitivity on tongue swabs than sputum-based molecular tests. C_LIO_LIRecent studies highlight that less sensitive non-sputum tests could have similar or even higher diagnostic yield due to the increased likelihood of people offered testing being able to provide a sample. C_LIO_LINo previous studies have directly compared the TB diagnostic yield of tongue swabs to sputum. C_LI Added value of this studyO_LIThis is the first comparative study of the diagnostic yield of tongue swab- vs. sputum-based molecular testing, conducted in real-world clinical settings across four high TB burden countries. C_LIO_LIUsing a low-cost molecular platform, we found that tongue swabs achieved similar diagnostic yield to sputum, with differences within a pre-specified non-inferiority margin. C_LIO_LINotably, tongue swabs were successfully collected from nearly all participants, including children and people living with HIV--groups in whom sputum collection can be especially difficult. C_LI Implications of all the available evidenceO_LITB diagnostic yield from tongue swabs is non-inferior to sputum-based molecular testing, demonstrating the value of tongue swabs as a viable and potentially lower-cost alternative to sputum for TB diagnosis. C_LIO_LIThese findings support further scale up and operational research to integrate tongue swab testing into TB diagnostic algorithms, particularly in settings where sputum collection is challenging, or smear microscopy remains the primary diagnostic method. C_LI