ABSTRACT
Tuberculosis (TB) still tops the list of global health burdens even after COVID-19. However, it will sooner transcend the current pandemic due to the prevailing risk of reactivation of latent TB in immunocompromised individuals. The indiscriminate misuse and overuse of antibiotics have resulted in the emergence of deadly drug-resistant variants of Mycobacterium tuberculosis (M.tb). This study aims to characterize the functionality of the carbapenem antibiotic-Biapenem (BPM) in generating long-lasting immunity against TB. BPM treatment significantly boosted the activation status of the innate immune arm-macrophages by augmenting p38 signaling. Macrophages further primed and activated the adaptive immune cells CD4+ and CD8+ T-cells in the lung and spleen of the infected mice model. Furthermore, BPM treatment significantly amplified the polarization of T lymphocytes toward inflammatory subsets, such as Th1 and Th17. The treatment also helped generate a long-lived central memory T-cell subset. The generation of central memory T lymphocyte subset upon BPM treatment in the murine model led to a significant curtailing in the recurrence of TB due to reactivation and reinfection. These results suggest the potentiality of BPM as a potent adjunct immunomodulator to improve host defense against M.tb by enriching long-term protective memory cells. IMPORTANCE Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) tops the list of infectious killers around the globe. The emergence of drug-resistant variants of M.tb has been a major hindrance toward realizing the "END TB" goal. Drug resistance has amplified the global burden toward the quest for novel drug molecules targeting M.tb. Host-directed therapy (HDT) offers a lucrative alternative to tackle emerging drug resistance and disease relapse by strengthening the host's immunity. Through our present study, we have tried to characterize the functionality of the carbapenem antibiotic-Biapenem (BPM). BPM treatment significantly augmented long-lasting immunity against TB by boosting the innate and adaptive immune arms. The generation of long-lived central memory T lymphocyte subset significantly improved the disease outcome and provided sterilizing immunity in the murine model of TB. The present investigation's encouraging results have helped us depict BPM as a potent adjunct immunomodulator for treating TB.
ABSTRACT
BACKGROUND: Non-invasive respiratory support for neonates using bubble continuous positive airway pressure (bCPAP) delivery systems is now widespread owing to its safety, cost effectiveness and easy applicability. Many innovative solutions have been suggested to deal with the possible shortage in desperate situations like disasters, pandemics and resource-limited settings. Although splitting of invasive ventilation has been reported previously, no attempts to split non-invasive respiratory support have been reported. OBJECTIVE: The primary objective was to test the feasibility of splitting the bCPAP assembly using a T-piece splitter in a simulation model. METHODS: A pilot simulation-based study was done to split a single bCPAP assembly using a T-piece. Other materials consisted of a heated humidification system, an air oxygen blender, corrugated inspiratory and expiratory tubing, nasal interfaces and two intercostal chest tube drainage bags. Two pressure manometers were used simultaneously to measure delivered pressures at different levels of set bCPAPs at the expiratory limb of nasal interfaces. RESULTS: Pressures measured at the expiratory end of two nasal interfaces were 5.1 and 5.2 cm H2O, respectively, at a flow of 6 L/min and a water level of 5 cm H2O in both chest bags. When tested across different levels of set continuous positive airway pressure (3-8 cmH2O) and fractional inspired oxygen concentration (0.30-1.0), measured parameters corresponded to set parameters. CONCLUSION: bCPAP splitting using a T-piece splitter is a technically simple, feasible and reliable strategy tested in a simulation model. Further testing is needed in a simulated lung model.