Implementing molecular tuberculosis diagnostic methods in limited-resource and high-burden countries.

Tuberculosis (TB) is one of the deadliest infectious diseases in the world with more than a million people dying of TB each year. Accurate and timely TB diagnosis has the potential to alleviate the global TB burden; therefore, one of the pillars of the End TB Strategy developed by the World Health Organization (WHO) is the early diagnosis of TB, including universal drug-susceptibility testing (DST). The WHO emphasises the importance of DST before treatment initiation, using molecular WHO-recommended rapid diagnostic tests (mWRDs). Currently available mWRDs are nucleic acid amplification tests, line probe assays, whole genome sequencing, and targeted next-generation sequencing. However, implementing the sequencing mWRDs in routine laboratories in low-income countries is constrained by the existing infrastructure, high cost, the specialised skills needed, data storage, and the current delay in results compared with other routine methods. These limitations are pronounced in resource-limited settings, which often have a high TB burden and need for innovative TB diagnostic technologies. In this article we propose several possible solutions, like adapting infrastructure capacity to needs, advocating for lowering costs, building bioinformatics and laboratory capacity, and increasing the use of open-access resources for software and publications.

Fast and noninvasive electronic nose for sniffing out COVID-19 based on exhaled breath-print recognition.

The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) approach has been widely used to detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, instead of using it alone, clinicians often prefer to diagnose the coronavirus disease 2019 (COVID-19) by utilizing a combination of clinical signs and symptoms, laboratory test, imaging measurement (e.g., chest computed tomography scan), and multivariable clinical prediction models, including the electronic nose. Here, we report on the development and use of a low cost, noninvasive method to rapidly sniff out COVID-19 based on a portable electronic nose (GeNose C19) integrating an array of metal oxide semiconductor gas sensors, optimized feature extraction, and machine learning models. This approach was evaluated in profiling tests involving a total of 615 breath samples composed of 333 positive and 282 negative samples. The samples were obtained from 43 positive and 40 negative COVID-19 patients, respectively, and confirmed with RT-qPCR at two hospitals located in the Special Region of Yogyakarta, Indonesia. Four different machine learning algorithms (i.e., linear discriminant analysis, support vector machine, stacked multilayer perceptron, and deep neural network) were utilized to identify the top-performing pattern recognition methods and to obtain a high system detection accuracy (88-95%), sensitivity (86-94%), and specificity (88-95%) levels from the testing datasets. Our results suggest that GeNose C19 can be considered a highly potential breathalyzer for fast COVID-19 screening.