SMaRT-PCR: Sampling with Mask and Reverse Transcriptase PCR, a promising non-invasive diagnostic tool for paediatric pulmonary tuberculosis

Abstract

AbstractPurposeDiagnostic challenges in pediatric TB, like difficulties obtaining sputum, need for invasive sampling, and suboptimal sensitivity of existing detection tools, advocate for sputum-free, child-friendly, and diagnostically accurate methods. This proof-of-concept study evaluates the diagnostic potential of non-invasivelysampling patient bioaerosols using a mask combined with reverse transcriptase (RT)PCR (SMaRT-PCR) for pediatric TB detection.MethodsIn this case-control study, we recruited 51 children (30 confirmed TB and 21 without TB) aged 2-15. Exhaled bioaerosols were captured on gelatin membrane-layered N-95 masks in a 10-minute process that involved talking, coughing, and breathing. Two mask samples were consecutively collected from children with TB and tested using GeneXpert and in-house RT-PCR for16sandrpoBRNA. The control cohort underwent single mask sampling and testing with RT-PCR. Mask sampling acceptability was assessed using a questionnaire and a Likert-scale.ResultsThe sensitivity and specificity of SMaRT-PCR for detecting16sandrpoBamong 24 treatment naïve patients were 75% and 95%, respectively, comparable to GeneXpert testing in standard samples from the same patients. Mask sampling with GeneXpert had sensitivity of only 13%. Over 90% of children were comfortable with mask sampling, and > 80% were happy or very happy on the Likert scale with the procedure.ConclusionThis is the first study to provide evidence for testing patient bioaerosols as a promising alternative for detecting pediatric TB. SMaRT-PCR has potential in a hub-and-spoke model, where samples collected from remote locations can be centrally tested by RT-PCR at district-level laboratories, enabling equitable access to diagnostic care.