THIS REPORT UPDATES PREVIOUS CDC GUIDELINES AND RECOMMENDATIONS ON PREFERRED PREVENTION AND TREATMENT REGIMENS REGARDING NATURALLY OCCURRING ANTHRAX. ALSO PROVIDED ARE A WIDE RANGE OF ALTERNATIVE REGIMENS TO FIRST-LINE ANTIMICROBIAL DRUGS FOR USE IF PATIENTS HAVE CONTRAINDICATIONS OR INTOLERANCES OR AFTER A WIDE-AREA AEROSOL RELEASE OF: Bacillus anthracis spores if resources become limited or a multidrug-resistant B. anthracis strain is used (Hendricks KA, Wright ME, Shadomy SV, et al.; Workgroup on Anthrax Clinical Guidelines. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014;20:e130687; Meaney-Delman D, Rasmussen SA, Beigi RH, et al. Prophylaxis and treatment of anthrax in pregnant women. Obstet Gynecol 2013;122:885-900; Bradley JS, Peacock G, Krug SE, et al. Pediatric anthrax clinical management. Pediatrics 2014;133:e1411-36). Specifically, this report updates antimicrobial drug and antitoxin use for both postexposure prophylaxis (PEP) and treatment from these previous guidelines best practices and is based on systematic reviews of the literature regarding 1) in vitro antimicrobial drug activity against B. anthracis; 2) in vivo antimicrobial drug efficacy for PEP and treatment; 3) in vivo and human antitoxin efficacy for PEP, treatment, or both; and 4) human survival after antimicrobial drug PEP and treatment of localized anthrax, systemic anthrax, and anthrax meningitis. CHANGES FROM PREVIOUS CDC GUIDELINES AND RECOMMENDATIONS INCLUDE AN EXPANDED LIST OF ALTERNATIVE ANTIMICROBIAL DRUGS TO USE WHEN FIRST-LINE ANTIMICROBIAL DRUGS ARE CONTRAINDICATED OR NOT TOLERATED OR AFTER A BIOTERRORISM EVENT WHEN FIRST-LINE ANTIMICROBIAL DRUGS ARE DEPLETED OR INEFFECTIVE AGAINST A GENETICALLY ENGINEERED RESISTANT: B. anthracis strain. In addition, these updated guidelines include new recommendations regarding special considerations for the diagnosis and treatment of anthrax meningitis, including comorbid, social, and clinical predictors of anthrax meningitis. The previously published CDC guidelines and recommendations described potentially beneficial critical care measures and clinical assessment tools and procedures for persons with anthrax, which have not changed and are not addressed in this update. In addition, no changes were made to the Advisory Committee on Immunization Practices recommendations for use of anthrax vaccine (Bower WA, Schiffer J, Atmar RL, et al. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices, 2019. MMWR Recomm Rep 2019;68[No. RR-4]:1-14). The updated guidelines in this report can be used by health care providers to prevent and treat anthrax and guide emergency preparedness officials and planners as they develop and update plans for a wide-area aerosol release of B. anthracis.

Abstract Bacillus cereus group bacteria containing the anthrax toxin genes can cause fatal anthrax pneumonia in welders. Two welder's anthrax cases identified in 2020 were investigated to determine the source of each patient's exposure. Environmental sampling was performed at locations where each patient had recent exposure to soil and dust. Samples were tested for the anthrax toxin genes by real-time PCR, and culture was performed on positive samples to identify whether any environmental isolates matched the patient's clinical isolate. A total of 185 environmental samples were collected in investigation A for patient A and 108 samples in investigation B for patient B. All samples from investigation B were real-time PCR-negative, but 14 (8%) samples from investigation A were positive, including 10 from patient A's worksite and 4 from his work-related clothing and gear. An isolate genetically matching the one recovered from patient A was successfully cultured from a worksite soil sample. All welder's anthrax cases should be investigated to determine the source of exposure, which may be linked to their worksite. Welding and metalworking employers should consider conducting a workplace hazard assessment and implementing controls to reduce the risk of occupationally associated illnesses including welder's anthrax.

Anthrax has been feared for its high mortality in animals and humans for centuries. The etiologic agent is considered a potentially devastating bioweapon, and since 1876-when Robert Koch demonstrated that Bacillus anthracis caused anthrax-it has been considered the sole cause of the disease. Anthrax is, however, a toxin-mediated disease. The toxins edema toxin and lethal toxin are formed from protein components encoded for by the pXO1 virulence plasmid present in pathogenic B. anthracis strains. However, other members of the Bacillus cereus group, to which B. anthracis belongs, have recently been shown to harbor the pXO1 plasmid and produce anthrax toxins. Infection with these Bacillus cereus group organisms produces a disease clinically similar to anthrax. This suggests that anthrax should be defined by the exotoxins encoded for by the pXO1 plasmid rather than the bacterial species it has historically been associated with, and that the definition of anthrax should be expanded to include disease caused by any member of the B. cereus group containing the toxin-producing pXO1 plasmid or anthrax toxin genes specifically.

Since 1997, nine cases of severe pneumonia, caused by species within the B. cereus group and with a presentation similar to that of inhalation anthrax, were reported in seemingly immunocompetent metalworkers, with most being welders. In seven of the cases, isolates were found to harbor a plasmid similar to the B. anthracis pXO1 that encodes anthrax toxins. In this paper, we review the literature on the B. cereus group spp. pneumonia among welders and other metalworkers, which we term welder’s anthrax. We describe the epidemiology, including more information on two cases of welder’s anthrax in 2020. We also describe the health risks associated with welding, potential mechanisms of infection and pathological damage, prevention measures according to the hierarchy of controls, and clinical and public health considerations. Considering occupational risk factors and controlling exposure to welding fumes and gases among workers, according to the hierarchy of controls, should help prevent disease transmission in the workplace. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Naturally occurring anthrax disproportionately affects the health and economic welfare of poor, rural communities in anthrax-endemic countries. However, many of these countries have limited anthrax prevention and control programs. Effective prevention of anthrax outbreaks among humans is accomplished through routine livestock vaccination programs and prompt response to animal outbreaks. The Centers for Disease Control and Prevention uses a 2-phase framework when providing technical assistance to partners in anthrax-endemic countries. The first phase assesses and identifies areas for improvement in existing human and animal surveillance, laboratory diagnostics, and outbreak response. The second phase provides steps to implement improvements to these areas. We describe examples of implementing this framework in anthrax-endemic countries. These activities are at varying stages of completion; however, the public health impact of these initiatives has been encouraging. The anthrax framework can be extended to other zoonotic diseases to build on these efforts, improve human and animal health, and enhance global health security.

Anthrax postexposure prophylaxis (PEP) was recommended to 42 people after a laboratory incident that involved potential aerosolization of Bacillus anthracis spores in 2 laboratories at the Centers for Disease Control and Prevention in 2014. At least 31 (74%) individuals who initiated PEP did not complete either the recommended 60 days of antimicrobial therapy or the 3-dose vaccine regimen. Among the 29 that discontinued the antimicrobial component of PEP, most (38%) individuals discontinued PEP because of their low perceived risk of infection; 9 (31%) individuals discontinued prophylaxis due to PEP-related minor adverse events, and 10% cited both low risk and adverse events as their reason for discontinuation. Most minor adverse events reported were gastrointestinal complaints, and none required medical attention. Individuals taking ciprofloxacin were twice as likely (RR = 2.02, 95% CI = 1.1-3.6) to discontinue antimicrobial prophylaxis when compared to those taking doxycycline. In the event anthrax PEP is recommended, public health messages and patient education materials will need to address potential misconceptions regarding exposure risk and provide information about possible adverse events in order to promote PEP adherence.

In 2014, CDC published updated guidelines for the prevention and treatment of anthrax (Hendricks KA, Wright ME, Shadomy SV, et al. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014;20[2]. Available at http://wwwnc.cdc.gov/eid/article/20/2/13-0687_article.htm). These guidelines provided recommended best practices for the diagnosis and treatment of persons with naturally occurring or bioterrorism-related anthrax in conventional medical settings. An aerosolized release of Bacillus anthracis spores over densely populated areas could become a mass-casualty incident. To prepare for this possibility, the U.S. government has stockpiled equipment and therapeutics (known as medical countermeasures [MCMs]) for anthrax prevention and treatment. However, previously developed, publicly available clinical recommendations have not addressed the use of MCMs or clinical management during an anthrax mass-casualty incident, when the number of patients is likely to exceed the ability of the health care infrastructure to provide conventional standards of care and supplies of MCMs might be inadequate to meet the demand required. To address this gap, in 2013, CDC conducted a series of systematic reviews of the scientific literature on anthrax to identify evidence that could help clinicians and public health authorities set guidelines for intravenous antimicrobial and antitoxin use, diagnosis of anthrax meningitis, and management of common anthrax-specific complications in the setting of a mass-casualty incident. Evidence from these reviews was presented to professionals with expertise in anthrax, critical care, and disaster medicine during a series of workgroup meetings that were held from August 2013 through March 2014. In March 2014, a meeting was held at which 102 subject matter experts discussed the evidence and adapted the existing best practices guidance to a clinical use framework for the judicious, efficient, and rational use of stockpiled MCMs for the treatment of anthrax during a mass-casualty incident, which is described in this report. This report addresses elements of hospital-based acute care, specifically antitoxins and intravenous antimicrobial use, and the diagnosis and management of common anthrax-specific complications during a mass-casualty incident. The recommendations in this report should be implemented only after predefined triggers have been met for shifting from conventional to contingency or crisis standards of care, such as when the magnitude of cases might lead to impending shortages of intravenous antimicrobials, antitoxins, critical care resources (e.g., chest tubes and chest drainage systems), or diagnostic capability. This guidance does not address primary triage decisions, anthrax postexposure prophylaxis, hospital bed or workforce surge capacity, or the logistics of dispensing MCMs. Clinicians, hospital administrators, state and local health officials, and planners can use these recommendations to assist in the development of crisis protocols that will ensure national preparedness for an anthrax mass-casualty incident.

Concern about use of anthrax as a bioweapon prompted development of novel anthrax antitoxins for treatment. Clinical guidelines for the treatment of anthrax recommend antitoxin therapy in combination with intravenous antimicrobials; however, a large-scale or mass anthrax incident may exceed antitoxin availability and create a need for judicious antitoxin use. We conducted a systematic review of antitoxin treatment of inhalation anthrax in humans and experimental animals to inform antitoxin recommendations during a large-scale or mass anthrax incident. A comprehensive search of 11 databases and the FDA website was conducted to identify relevant animal studies and human reports: 28 animal studies and 3 human cases were identified. Antitoxin monotherapy at or shortly after symptom onset demonstrates increased survival compared to no treatment in animals. With early treatment, survival did not differ between antimicrobial monotherapy and antimicrobial-antitoxin therapy in nonhuman primates and rabbits. With delayed treatment, antitoxin-antimicrobial treatment increased rabbit survival. Among human cases, addition of antitoxin to combination antimicrobial treatment was associated with survival in 2 of the 3 cases treated. Despite the paucity of human data, limited animal data suggest that adjunctive antitoxin therapy may improve survival. Delayed treatment studies suggest improved survival with combined antitoxin-antimicrobial therapy, although a survival difference compared with antimicrobial therapy alone was not demonstrated statistically. In a mass anthrax incident with limited antitoxin supplies, antitoxin treatment of individuals who have not demonstrated a clinical benefit from antimicrobials, or those who present with more severe illness, may be warranted. Additional pathophysiology studies are needed, and a point-of-care assay correlating toxin levels with clinical status may provide important information to guide antitoxin use during a large-scale anthrax incident.

We reviewed the published findings from the Texas Neural Tube Defect Project, a 6-year case-control study (1995-2000) of neural tube defects (NTDs) on the Texas-Mexico border. In this review, we highlight what was learned about environmental, genetic, and nutritional factors (i.e., those related to the folate and other metabolic pathways) and the novel putative risk factors that emerged from this study of Mexican American women living on the Texas-Mexico border. Our investigations of the micronutrients and metabolic pathways involved confirmed the findings of other researchers that increased folate intake has a protective effect and that low serum B(12) , high serum homocysteine levels, and obesity independently contribute to risk. Studies of this population also have implicated hyperinsulinemia and low ferritin, metabolic risk factors, which require additional study to elucidate their physiologic mechanism. Environmental contaminants such as heavy metals, pesticides, and polychlorinated biphenyls (PCBs), which were of community concern, did little to explain NTD risk. Studies in this folic acid deficit-population also revealed several novel risk factors, namely, diarrhea, stress, fumonisins, and the combination of nitrosatable drug exposure with high nitrate/nitrite intake. In conclusion, the 23 studies among the Mexican American women living along the Texas-Mexico border have demonstrated the multifactorial nature of NTDs and that a population deficient in folic acid will be vulnerable to a variety of insults whether brought on by individual behaviors (e.g., obesity) or through the surrounding environment (e.g., fumonisins). (Birth Defects Research (Part A), 2012. (c) 2012 Wiley Periodicals, Inc.)