Responding to the Threat Posed by Anthrax: Updated Evidence to Improve Preparedness

For many Americans, awareness of the threat posed by anthrax is closely tied to the attacks of October 2001 and November 2001 when 22 persons were diagnosed with anthrax from exposure to intentionally contaminated mail [1]. That event highlighted the critical need to strengthen preparedness for this biothreat in the United States. Anthrax is a bacterial disease caused by Bacillus anthracis. The US Department of Health and Human Services designated B. anthracis as a tier 1 select agent, signifying that it presents the greatest risk of deliberate misuse with significant potential for mass causalities and poses a severe threat to public health and safety [2].

Worldwide, most anthrax results from contact with or consumption of infected animals, leading to cutaneous and gastrointestinal disease. In the nineteenth to mid-twentieth century, a new form of anthrax became a problem for workers in textile mills who handled and processed animal hair contaminated with anthrax spores. This form of anthrax—inhalation anthrax—became known as woolsorter’s disease. In response to this occupational concern, an acellular anthrax vaccine was developed in 1954 and evaluated in US textile mill workers [3]. This early vaccine was later developed into the anthrax vaccine adsorbed, which remains one of our major medical countermeasures today [4].

Events such as the accidental release of spores from a Soviet Union military facility, which resulted in at least 66 fatalities in 1979 [5], an unsuccessful anthrax attack by the Aum Shinrikyo cult in Japan in 1993 [6], and Iraq’s biological warfare program leading up to and during the Gulf War that included development of bombs and warheads filled with B. anthracis [7, 8] have heightened concerns of bioterrorism. In response to these and other events, the following measures were implemented: in 1998, the US military began vaccinating soldiers deploying to certain areas of the world; in 1999, the Laboratory Response Network [9] and the National Pharmaceutical Stockpile, now known as the Strategic National Stockpile [10], were established; and new countermeasures were developed, including polyclonal and monoclonal antitoxins [11]. Although developed in response to bioterrorism concerns, these antitoxins have been used to treat rare naturally acquired cases and newly described forms of anthrax, including injection anthrax and welder’s anthrax (frequently fatal pneumonias caused by other Bacillus species expressing anthrax toxins). The potential for B. anthracis to be weaponized, including the possibility that a strain could be genetically engineered to resist 1 or more classes of antimicrobials, continues to be a concern. These possibilities led the Centers for Disease Control and Prevention to update clinical guidelines for prevention and treatment of anthrax in 2014 [12–14]. This supplement is a compilation of articles that establishes a more robust evidence base than was available in 2014 for an update to anthrax postexposure prophylaxis (PEP) and treatment guidelines. Thus, the cycle of public health advancing preparedness and preparedness efforts improving public health continues.

This supplement includes 15 articles about anthrax that review its clinical features [15], optimal antimicrobial treatment and PEP [16–21], and the value and use of antitoxins [18, 22–25]. This supplement also proposes methods to rapidly identify and optimally treat anthrax meningitis [18, 26–29]. Answering questions related to a disease as serious and, fortunately, rare as systemic anthrax requires a multipronged approach. The comprehensive data presented in this supplement are derived from in vitro studies, animal models, and reviews of human cases with inclusion dates ranging from as early as 1880 to as late as 2019.

These efforts will allow us to provide better guidance on optimal antimicrobial use for treatment or PEP based on drug safety data [21], in vitro performance [16], and in vivo data looking at use of bactericidal and protein synthesis inhibitor drugs singly or in combination [17, 18]. The drugs that may be most useful if naturally occurring or engineered antimicrobial resistant strains are encountered were also evaluated [16, 17]. For systemic anthrax, several articles assess effectiveness of monoclonal or polyclonal antitoxins as PEP or treatment in humans or animals [18, 24, 25], including humans infected with non-B. anthracis species expressing anthrax toxin (eg, welder’s anthrax caused by Bacillus tropicus) [22].

Finally, several reports augment existing knowledge about the clinical features of anthrax, detailing the frequency of complications associated with each type of anthrax [15], the variation in presentation and outcomes in children vs adults [15], and the difficulty of identifying and successfully treating anthrax meningitis [18, 26, 27]. This includes the development and evaluation of a triage tool to help identify anthrax meningitis based on signs and symptoms [28, 29].

Preparedness against intentional use of B. anthracis and occupational or environmental exposures to B. anthracis relies on clinical guidance that incorporates all available countermeasures including new antimicrobials and advances in critical care. The armamentarium for PEP and treatment of anthrax includes several effective antimicrobials, including options for resistant strains, antitoxins, and vaccines [30]. The severity of disease and antimicrobial safety in the specific population(s) affected should guide treatment and/or PEP decisions. Collectively, the reviews and research in this supplement enhance anthrax preparedness, strengthen national public health security, and advance scientific and medical knowledge.

Notes

Acknowledgments . This supplement is the product of considerable effort by federal partners, national and international anthrax experts, clinicians, fellows, and academic investigators. The authors thank all contributors for their valuable work.

Disclaimer . The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC or other USG agencies, including the US Army.

Financial support . This project was supported by the Centers for Disease Control and Prevention and the Office of the Assistant Secretary for Preparedness and Response.

Supplement sponsorship . This article appears as part of the supplement “Anthrax Preparedness,” sponsored by the Centers for Disease Control and Prevention.

Potential conflicts of interest . All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.