RESUMEN
Tuberculosis (TB) remains a significant global health issue; making early, accurate, and inexpensive point-of-care detection critical for effective treatment. This paper presents a clinical demonstration of an electrochemical sensor that detects methyl-nicotinate (MN), a volatile organic biomarker associated with active pulmonary tuberculosis. The sensor was initially tested on a patient cohort comprised of 57 adults in Kampala, Uganda, of whom 42 were microbiologically confirmed TB-positive and 15 TB-negative. The sensor employed a copper(II) liquid metal salt solution with a square wave voltammetry method tailored for MN detection using commercially available screen-printed electrodes. An exploratory machine learning analysis was performed using XGBOOST. Utilizing this approach, the sensor was 78% accurate with 71% sensitivity and 100% specificity. These initial results suggest the sensing methodology is effective in identifying TB from complex breath samples, providing a promising tool for non-invasive and rapid TB detection in clinical settings.
RESUMEN
BACKGROUND: Sputum-based testing is a barrier to increasing access to molecular diagnostics for tuberculosis (TB). Many people with TB are unable to produce sputum, and sputum processing increases assay complexity and cost. Tongue swabs are emerging as an alternative to sputum, but performance limits are uncertain. METHODS: From June 2022 to July 2023, we enrolled 397 consecutive adults with cough >2 weeks at 2 health centers in Kampala, Uganda. We collected demographic and clinical information, sputum for TB testing (Xpert MTB/RIF Ultra and 2 liquid cultures), and tongue swabs for same-day quantitative polymerase chain reaction (qPCR) testing. We evaluated tongue swab qPCR diagnostic accuracy versus sputum TB test results, quantified TB targets per swab, assessed the impact of serial swabbing, and compared 2 swab types (Copan FLOQSWAB and Steripack spun polyester). RESULTS: Among 397 participants, 43.1% were female, median age was 33 years, 23.5% were diagnosed with human immunodeficiency virus, and 32.0% had confirmed TB. Sputum Xpert Ultra and tongue swab qPCR results were concordant for 98.2% (95% confidence interval [CI]: 96.2-99.1) of participants. Tongue swab qPCR sensitivity was 92.6% (95% CI: 86.5 to 96.0) and specificity was 99.1% (95% CI: 96.9 to 99.8) versus microbiological reference standard. A single tongue swab recovered a 7-log range of TB copies, with a decreasing recovery trend among 4 serial swabs. Swab types performed equivalently. CONCLUSIONS: Tongue swabs are a promising alternative to sputum for molecular diagnosis of TB, with sensitivity approaching sputum-based molecular tests. Our results provide valuable insights for developing successful tongue swab-based TB diagnostics.
Asunto(s)
Mycobacterium tuberculosis , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Manejo de Especímenes , Esputo , Lengua , Humanos , Femenino , Esputo/microbiología , Masculino , Uganda , Adulto , Lengua/microbiología , Manejo de Especímenes/métodos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Tuberculosis/diagnóstico , Tuberculosis/microbiología , Persona de Mediana Edad , Adulto Joven , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/microbiologíaRESUMEN
Background: Reliance on sputum-based testing is a key barrier to increasing access to molecular diagnostics for tuberculosis (TB). Many people with TB are unable to produce and sputum processing increases the complexity and cost of molecular assays. Tongue swabs are emerging as an alternative to sputum, but performance limits are uncertain. Methods: From June 2022 to July 2023, we enrolled 397 consecutive adults with cough >2 weeks at two health centers in Kampala, Uganda. We collected routine demographic and clinical information, sputum for routine TB testing (one Xpert MTB/RIF Ultra® and two liquid cultures), and up to four tongue swabs for same-day qPCR. We evaluated tongue swab qPCR diagnostic accuracy in reference to sputum TB test results, quantified TB targets per swab, assessed the impact of serial swabbing, and compared two swab types (Copan FLOQSWAB® and Steripack® spun polyester swabs). Results: Among 397 participants, 43.1% were female, median age was 33 years, 23.5% were living with HIV (PLHIV) and 32.3% had confirmed TB. Sputum Xpert Ultra and tongue swab qPCR results were concordant for 98.2% [96.2-99.1] of participants. Tongue swab qPCR sensitivity was 91.0% [84.6-94.9] and specificity 98.9% [96.2-99.8] vs. microbiological reference standard (MRS). A single tongue swab recovered a seven-log range of TB copies, with a decreasing recovery trend among four serial swabs. We found no difference between swab types. Conclusions: Tongue swabs show promise as an alternative to sputum for TB diagnosis, with sensitivity approaching sputum-based molecular tests. Our results provide valuable insights for developing successful tongue swab-based TB diagnostics.