Invasive B. anthracis infection is a relatively rare but highly lethal infection in humans. Production of lethal and edema toxin are believed to be central to the pathogenesis of B. anthracis infection. Due to the infrequency of invasive B. anthracis infection, but its potential use as a weapon of bioterror, the FDA permits the evaluation and approval of adjunctive therapy of this infection based on studies performed in at least two clinically relevant animal models. To what extent models that have been used to date to test anti-toxin agents have simulated the conditions encountered in patients presenting with invasive anthrax infection is unclear. Also, whether the effectiveness of anti-toxin agents is influenced when conditions do approach those encountered clinically (e.g. treatment after infection has manifested itself and in combination with other therapies) has not been investigated. To address these questions we are performing a systematic review of the literature and a meta-analysis of all preclinical models employing live B. anthracis challenge and testing anthrax anti-toxin treatments with or without accompanying antibiotic support. With this analysis, we aim to establish how closely such anti-toxin therapies have been tested pre-clinically when compared to the use of such agents clinically and whether the effectiveness of these agents change when clinical conditions are closely simulated.
| Xu, Wanying; Ohanjanian, Lernik; Sun, Junfeng et al. (2017) A systematic review and meta-analysis of preclinical trials testing anti-toxin therapies for B. anthracis infection: A need for more robust study designs and results. PLoS One 12:e0182879 |
