eNose-TB: A trial study protocol of electronic nose for tuberculosis screening in Indonesia

Abstract

Background: Even though conceptually, Tuberculosis (TB) is almost always curable, it is currently the world's leading infectious killer. Patients with pulmonary TB are the source of transmission. Approximately 23% of the world's population is believed to be latently infected with TB bacteria, and 5-15% of them will progress at any point in time to develop the disease. There was a global diagnostic gap of 2.9 million between notifications of new cases and the estimated number of incident cases, and Indonesia carries the third-highest of this gap. Therefore, screening TB among the community is of great importance to prevent further transmission and infection. The electronic nose for screening TB (eNose-TB) project is initiated in Yogyakarta, Indonesia, to screen TB by breath test with an electronic-nose that is easy-to-use, point-of-care, does not expose patients to radiation, and can be produced at low cost.

Methods/design: The objectives of the two-phase planned project are to: 1) investigate the potential of an eNose-TB as a screening tool in Indonesia, in comparison with screening with clinical symptoms and chest radiology, which are currently used as a standard, and 2) analyze the time and cost of a screening algorithm with eNose-TB to obtain additional case detection. A cross-sectional study will be conducted in the first phase to validate the eNose-TB. The validation phase will involve 395 presumptive TB patients in the Surakarta General Hospital, Central Java. In the second phase, a cross-sectional research will be conducted, involving 1,383 adults and children in the municipality of Yogyakarta and Kulon Progo district of Yogyakarta Province.

Discussion: The findings will provide data concerning the sensitivity and specificity of the eNose-TB as a screening tool for tuberculosis, and the time and cost analysis of a screening algorithm with the eNose.

Trial registration: NCT04567498; https://clinicaltrials.gov/.

Fig 1. ROC curve of the best model in diagnostic sensitivity and specificity of breath test in the training phase.

ROC = Receiver Operating Characteristic.

Fig 2. Flowchart of the validation phase of the eNose-TB in diagnosing TB.

Fig 3. Flowchart of screening with the eNose-TB, clinical symptoms, and chest radiography.

Fig 4. The lab-made eNose-TB device connected to the sampling bag through a mouthpiece and HEPA filter.

Fig 5. Schematic circuit of the eNose-TB system.

Fig 6. The response of 16 sensors of eNose-TB for negative TB (a) and positive TB (b) subjects.

Fig 7. Change of temperature (a) and relative humidity (b) in the sensor chamber during the measurement.