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Yersinia pestis is the causative agent of plague and is considered one of the most likely pathogens to be used as a bioweapon. In humans, plague is a severe clinical infection that can rapidly progress with a high mortality despite antibiotic therapy. Therefore, early treatment of Y. pestis infection is crucial. This review provides an overview of its clinical manifestations, diagnosis, treatment, prophylaxis, and protection requirements for the use of clinicians. We discuss the likelihood of a deliberate release of plague and the feasibility of obtaining, isolating, culturing, transporting and dispersing plague in the context of an attack aimed at a westernized country. The current threat status and the medical and public health responses are reviewed. We also provide a brief review of the potential prehospital treatment strategy and vaccination against Y. pestis. Further, we discuss the plausibility of antibiotic resistant plague bacterium, F1-negative Y. pestis, and also the possibility of a plague mimic along with potential strategies of defense against these. An extensive literature search on the MEDLINE, EMBASE, and Web of Science databases was conducted to collate papers relevant to plague and its deliberate release. Our review concluded that the deliberate release of plague is feasible but unlikely to occur, and that a robust public health response and early treatment would rapidly halt the transmission of plague in the population. Front-line clinicians should be aware of the potential of a deliberate release of plague and prepared to instigate early isolation of patients. Moreover, front-line clinicians should be weary of the possibility of suicide attackers and mindful of the early escalation to public health organizations.
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