Trained innate immunity and resistance to Mycobacterium tuberculosis infection.

BACKGROUND: Some individuals, even when heavily exposed to an infectious tuberculosis patient, develop neither active nor latent tuberculosis infection (LTBI). This 'early clearance' of Mycobacterium tuberculosis is associated with a history of bacillus Calmette-Guérin (BCG) vaccination. As BCG vaccination can boost innate immune responses through a process termed 'trained immunity', we hypothesize that BCG-induced trained innate immunity contributes to early clearance of M. tuberculosis. OBJECTIVES: We describe the epidemiological evidence and biological concepts of early clearance and trained immunity, and the possible relation between these two processes through BCG vaccination. SOURCES: Relevant data from published reports up to November 2018 were examined in the conduct of this review. CONTENT: Several observational studies and one recent randomized trial support the concept that boosting innate immunity contributes to protection against M. tuberculosis infection, with BCG vaccination providing approximately 50% protection. The molecular mechanisms mediating early clearance remain largely unknown, but we propose that trained immunity, characterized by epigenetic and metabolic reprogramming of innate immune cells such as monocytes or macrophages, is at least partially responsible for eliminating the mycobacteria and inducing early clearance. IMPLICATIONS: Future studies should examine if BCG revaccination increases early clearance of M. tuberculosis through induction of trained immunity. Epigenetic or metabolic modulation may further boost BCG-induced trained innate immunity to promote tuberculosis prevention. New tuberculosis vaccine candidates should also be examined for their capacity to improve protection against M. tuberculosis infection and induce trained immunity.

The emergence of community-onset Clostridium difficile infection in a tertiary hospital in Singapore: a cause for concern.

Increasing rates of Clostridium difficile infection (CDI) among those without traditional risk factors have been reported mainly in Europe and North America. Here we describe the epidemiology, clinical features and ribotypes of CDI at National University Hospital (NUH), a 1000-bed tertiary care hospital in Singapore, from December 2011 to May 2012. All laboratory-confirmed CDI cases ≥21 years old who gave informed consent were included. Clinical data were collected prospectively and participants underwent an interviewer-administered questionnaire. Cases were classified by healthcare facility exposure and severity according to the SHEA guidelines. Included cases were also subjected to PCR and were classified by ribotype. In total, 66 patients participated in the study, of which 33 (50.0%) were healthcare-facility-associated hospital onset (HCFA-HO). Of the 33 community-onset (CO) cases, 14 (42.4%) were HCFA-CO, 10 (30.3%) were indeterminate and 9 (27.3%) were community-associated (CA). Of the CA cases, a majority (90.9%) had prior exposure to a healthcare facility within the last 12 weeks. Clinical characteristics, exposures and outcomes were not different between HO-CDI and CO-CDI. Diagnosis was delayed in CO-CDI compared with HO-CDI (4 days vs. 1 day; P=0.014). There was no difference in distribution of ribotypes between CO-CDI and HO-CDI, with 053 being most prevalent in both groups. CO-CDI increasingly contributes to the burden of CDI in NUH. This may reflect a trend in other parts of Asia. Healthcare professionals should be aware of the possible role of outpatient healthcare environments to CDI risk and thus extend control measures to outpatient settings.