Current tools for screening LTBI are limited due to the long turnaround time required, cross-reactivity of tuberculin skin test to BCG vaccine and the high cost of interferon gamma release assay (IGRA) tests. We evaluated Raman spectroscopy (RS) for serum-protein fingerprinting from 26 active TB (ATB) cases, 20 LTBI cases, 34 early clearance (EC; TB-exposed persons with undetected infection) and 38 healthy controls (HC). RS at 532 nm using candidate peaks provided 92.31% sensitivity and 90.0% to distinguish ATB from LTBI, 84.62% sensitivity and 89.47% specificity to distinguish ATB from HC and 87.10% sensitivity and 85.0% specificity to distinguish LTBI from EC. RS at 532 nm with the random forest model provided 86.84% sensitivity and 65.0% specificity to distinguish LTBI from HC and 94.74% sensitivity and 87.10% specificity to distinguish EC from HC. Using preliminary sample sets (n = 5 for each TB-infection category), surface-enhanced Raman spectroscopy (SERS) showed high potential diagnostic performance, distinguishing very clearly among all TB-infection categories with 100% sensitivity and specificity. With lower cost, shorter turnaround time and performance comparable to that of IGRAs, our study demonstrated RS and SERS to have high potential for ATB and LTBI diagnosis.
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