Moral injury, mental health and behavioural health outcomes: A systematic review of the literature.

Despite a burgeoning of research on moral injury in the past decade, existing reviews have not explored the breadth of consequences and the multitude of pathways through which moral injury and potentially morally injurious experiences (PMIEs) influence mental and behavioural health outcomes. This study aimed to identify associations between moral injury on mental and behavioural health. Literature searches of psychological and medical databases were conducted through April 2020. Eligible studies measured moral injury or PMIEs, and health outcomes (e.g., depression, substance use and suicidality). Fifty-seven publications representing 49 separate samples were included. Studies examined the impact of moral injury on post-traumatic stress disorder (PTSD) (n = 43); depression (n = 32); anxiety (n = 15); suicide (n = 15); substance use (n = 14); and 'other' health outcomes, including pain, burnout, sleep disturbance and treatment-seeking behaviours (n = 11). The majority of studies found significant positive associations between moral injury-related constructs, mental health and behavioural health outcomes; however, the majority were also cross-sectional and focused on military samples. Proposed mediators included lack of social support, negative cognitions and meaning-making. Moderators included self-compassion, pre-deployment mental health education and mindfulness. Moral injury is associated with a variety of negative health outcomes. Research is needed to determine the mechanisms by which moral injury may influence these outcomes over time.

Validation of a Human Challenge Model Using an LT-Expressing Enterotoxigenic E. coli Strain (LSN03-016011) and Characterization of Potential Amelioration of Disease by an Investigational Oral Vaccine Candidate (VLA1701).

Controlled human infection models are important tools for the evaluation of vaccines against diseases where an appropriate correlate of protection has not been identified. Enterotoxigenic Escherichia coli (ETEC) strain LSN03-016011/A (LSN03) is an LT enterotoxin and CS17-expressing ETEC strain useful for evaluating vaccine candidates targeting LT-expressing strains. We sought to confirm the ability of the LSN03 strain to induce moderate-to-severe diarrhea in a healthy American adult population, as well as the impact of immunization with an investigational cholera/ETEC vaccine (VLA-1701) on disease outcomes. A randomized, double-blinded pilot study was conducted in which participants received two doses of VLA1701 or placebo orally, one week apart; eight days after the second vaccination, 30 participants (15 vaccinees and 15 placebo recipients) were challenged with approximately 5 × 109 colony-forming units of LSN03. The vaccine was well tolerated, with no significant adverse events. The vaccine also induced serum IgA and IgG responses to LT. After challenge, 11 of the placebo recipients (73.3%; 95%CI: 48.0-89.1) and 7 of the VLA1701 recipients (46.7%; 95%CI: 24.8-68.8) had moderate-to-severe diarrhea (p = 0.26), while 14 placebo recipients (93%) and 8 vaccine recipients (53.3%) experienced diarrhea of any severity, resulting in a protective efficacy of 42.9% (p = 0.035). In addition, the vaccine also appeared to provide protection against more severe diarrhea (p = 0.054). Vaccinees also tended to shed lower levels of the LSN03 challenge strain compared to placebo recipients (p = 0.056). In addition, the disease severity score was lower for the vaccinees than for the placebo recipients (p = 0.046). In summary, the LSN03 ETEC challenge strain induced moderate-to-severe diarrhea in 73.3% of placebo recipients. VLA1701 vaccination ameliorated disease severity, as observed by several parameters, including the percentage of participants experiencing diarrhea, as well as stool frequency and ETEC severity scores. These data highlight the potential value of LSN03 as a suitable ETEC challenge strain to evaluate LT-based vaccine targets (NCT03576183).