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 originally performed 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. This analysis suggested that animal models, while important for the investigation of the effects the B. anthracis toxins and agents directed against them, may have weaknesses that should be accounted for when considering the inclusion of such agents in the Strategic National Stockpile. That work was published in 2017. That original literature search is now being updated to determine whether more recent investigations have examined anti-toxin treatments in B. anthracis challenged animal models that have been supported with antibiotics. Research on this project is ongoing.
| 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 |
