Quantifying the contribution of smear-negative, culture-positive pulmonary tuberculosis to nosocomial transmission

Background Despite current guidelines for tuberculosis (TB) control in healthcare settings, which focused on smear-positive cases, prevention of nosocomial TB transmission continues to be a challenge. Here, we report results of the first hospital-wide prospective study applying interferon-gamma release assay to investigate the role of smear-negative, culture-positive index cases in nosocomial TB transmission. Methods We prospectively identified cases of culture-confirmed smear-negative pulmonary TB receiving aerosol-generating procedures (AGPs) and cases of culture-confirmed smear-positive pulmonary TB admitted at a medical center. Nosocomial transmission was evaluated by screening their close contacts for latent TB infection (LTBI) using interferon-gamma release assay. Results A total of 93 smear-negative index receiving AGP and 122 smear-positive index were enrolled. Among them, 13 (14.0%) and 43 (35.2%) index cases, respectively, had secondary cases of LTBI (p<0.001). Sputum smear negativity (adjusted odds ratio [aOR]: 0.20 [0.08–0.48]) and AGP (sputum suction; aOR: 3.48 [1.34–9.05]) are independent factors of transmission. A similar proportion in the close contacts of the two index groups had LTBI (17 [15.3%] and 63 [16.0%], respectively), and the former index group contributed to 21.3% of nosocomial transmission. Conclusion Smear-negative, culture-positive index cases receiving AGPs could be as infectious as smear-positive index cases. Hospital TB control policy should also focus on the former group.