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Background: Anthrax is a zoonotic disease caused by Bacillus anthracis that poses a significant threat to both human health and livestock. Effective preparedness and response to anthrax outbreak at the district level is essential to mitigate the devastating impact of the disease to humans and animals. The current diseaae surveillance in animals and humans uses two different infrastructure systems with online platform supported by established diagnostic facilities. The differences in surveillance systems affect timely outbreak response especially for zoonotic diseases like anthrax. We therefore aimed to assess the feasibility of implementing a simulation exercise for a potential anthrax outbreak in a local government setting and to raise the suspicion index of different district stakeholders for a potential anthrax outbreak in Namisindwa District, Uganda., Methods: We conducted a field-based simulation exercise and a health education intervention using quantitative data collection methods. The study participants mainly members of the District Taskforce (DTF) were purposively selected given their role(s) in disease surveillance and response at the sub-national level. We combined 26 variables (all dichotomized) assessing knowledge on anthrax and knowledge on appropriate outbreak response measures into an additive composite index. We then dichotomized overall score based on the 80% blooms cutoff i.e. we considered those scoring at least 80% to have high knowledge, otherwise low. We then assessed the factors associated with knowledge using binary logistic regression with time as a proxy for the intervention effect. Odds ratios (ORs) and 95% Confidence intervals (95%CI) have been reported., Results: The overall district readiness score was 35.0% (24/69) and was deficient in the following domains: coordination and resource mobilization (5/16), surveillance (5/11), laboratory capacity (3/10), case management (4/7), risk communications (4/12), and control measures (4/13). The overall community readiness score was 7 out of 32 (22.0%). We noted poor scores of readiness in all domains except for case management (2/2). The knowledge training did not have an effect on the overall readiness score, but improved specific domains such as control measures. Instead tertiary education was the only independent predictor of higher knowledge on anthrax and how to respond to it (OR = 1.57, 95% CI = 1.07-2.31). Training did not have a significant association with overall knowledge improvement but had an effect on several individual knowledge aspects., Conclusion: We found that the district's preparedness to respond to a potential anthrax outbreak was inadequate, especially in coordination and mobilisation, surveillance, case management, risk communication and control measures. The health education training intervention showed increased knowledge levels compared to the pre-test and post-test an indicator that the health education sessions could increase the index of suspicion. The low preparedness underscores the urgency to strengthen anthrax preparedness in the district and could have implications for other districts. We deduce that trainings of a similar nature conducted regularly and extensively would have better effects. This study's insights are valuable for improving anthrax readiness and safeguarding public and animal health in similar settings., (© 2024. The Author(s).)

Anthrax has re-emerged in domestic ruminants in Nigeria with public health concerns. This study assessed stakeholders' perceptions and preventive preparedness toward further resurgence and spread at the human-animal-environment interface. A questionnaire-based cross-sectional study was conducted in Nigeria. Descriptive and analytical statistical analyses were performed at 95% confidence levels. All the 384 recruited stakeholders responded. The majority (96.2%) of animal health practitioners (AHPs) and 56.7% of pastoralists were aware of the recent anthrax re-emergence in Nigeria (p < 0.001). Noteworthy, 88.5% of the AHPs and 32.2% of pastoralists mentioned that anthrax has an environmental component in its transmission to humans and animals. From the environmental perspective, 87.7% of AHPs and 24.0% of pastoralists significantly perceived that soil and aerosol contamination with anthrax spores are highly plausible explanation routes for its re-emergence. Extreme weather events (high rainfall, flooding, winds, and drought) (p = 0.001); grazing of livestock on pastures grown on contaminated soil (p < 0.001), transboundary movement and trade of animals (p = 0.001); introduction of new animals into the herds without quarantine (p = 0.001); and bioterrorism (p < 0.001) were more likely to influence the re-emergence and spread of anthrax. To tackle gaps in knowledge and risk perceptions, and address the socio-economic and anthropogenic drivers, cooperation and collaborations through the lens of the One Health approach are needed. The partnership will promote an integrated disease surveillance system from planning to implementation for the realization of elimination or reduction of the burden of anthrax and other zoonoses in Nigeria and contribute to achieving food safety, food security, and public and ecosystem health., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Anthrax is the most prioritized zoonotic disease in Kazakhstan due to its threatening potential to the public health and agricultural sector. Sporadic anthrax outbreaks are being reported annually among human and livestock populations throughout the country, with the highest frequency occurring in West Kazakhstan., Methods: A cross-sectional study was conducted using a survey-based face-to-face interview. From January to May 2022, 489 randomly selected participants were surveyed in 6 districts of the Baiterek province in West Kazakhstan oblast to evaluate the knowledge, attitude and practice (KAP) regarding anthrax among community members. This is the first KAP study conducted relating to outbreaks of anthrax in Kazakhstan., Results: In this study, most participants (74%) surveyed were males, and 40% of respondents had a secondary level education. Overall, 91% of the community respondents were engaged in agriculture and livestock rearing. Among these community members, cattle rearing was the most common (67%) occupation compared to other livestock species. Additionally, over a 50% of the population studied had no knowledge about the zoonotic nature of the disease, and about 82% and 87% of respondents were unaware of any animal and human anthrax symptoms, respectively. About 70% of the respondents were interested in vaccinating their livestock against anthrax. Individuals aged 45-54 displayed notably higher animal vaccination rates (45%; 95% CI: 38.4-52.0; p < 0.025) compared to those aged 25-34 and 65-74. Respondents residing in the Beles district (20%; 95% CI: 17.1-24.7; p < 0.005) exhibited a significantly higher level of awareness concerning the fatality of anthrax in contrast to participants from Bolashak. Roughly 61% of respondents held the belief that anthrax is a lethal disease. An overwhelming majority of the survey participants (99%) affirmed their non-participation in the slaughter of infected animals., Conclusion: The findings of this study indicate that KAP among community members relating to anthrax is low and requires swift implementation of education programmes in building awareness of anthrax under the One Health approach, especially in anthrax prone regions., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

The One Health approach calls for collaboration across various sectors and different scales to improve understanding of complex health issues. Regarding epidemiological surveillance, this implies the development of integrated systems that link several surveillance components operating in different domains (human, domestic animals, environment) and involving several actor networks. However, surveillance continues to operate in a very compartmentalized way, with little interaction between sectoral institutions and with the community for the governance and operation of surveillance activities. This is partly explained by the insufficient consideration of the local context and the late involvement of national stakeholders when developing programmes that aimed at strengthening the integration of surveillance. In low- and middle-income countries in particular, there is a strong influence of external partners on the development of intersectoral programmes, including surveillance systems. In this context, we developed and implemented a participatory planning process to support stakeholders of the surveillance system of anthrax in Burkina Faso, in the definition of the One Health surveillance system they wish for and of the pathway to reach it. The workshop produced an action plan that reflects the views and perspectives of representatives of the different categories of stakeholders and beneficiaries of surveillance. In addition, the participation of stakeholders in this participatory co-construction process has also improved their knowledge and mutual understanding, fostering a climate of trust conducive to further collaboration for surveillance activities. However, the quality of the participation raises some questions over the results, and contextual factors may have influenced the process. This underlines the need to include a monitoring and evaluation plan in the process to assess its implementation and ability to produce One Health surveillance modalities that are appropriate, accepted and applied over the long term., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Anthrax is reported with frequency but poorly understood in Southeast Asian countries including Vietnam. In Vietnam, anthrax surveillance is national. However, case detection, prevention, and control are implemented locally at the provincial level. Here, we describe the epidemiological characteristics, identify spatial clusters of human anthrax, and compare the variation in livestock anthrax vaccine coverage to disease incidence in humans and livestock using historical data in Son La province, Vietnam (2003-2020)., Methods and Results: Most human cases occurred between April and September. Most of the patients were male, aged 15-54 years old. The human cases were mainly reported by public district hospitals. There was a delay between disease onset and hospitalization of ~5 days. We identified spatial clusters of high-high incidence communes in the northern communes of the province using the local Moran's I statistic. The vaccine coverage sharply decreased across the study period. The province reported sporadic human anthrax outbreaks, while animal cases were only reported in 2005 and 2022., Conclusions: These results suggest underreporting for human and livestock anthrax in the province. Intersectoral information sharing is needed to aid livestock vaccination planning, which currently relies on reported livestock cases. The spatial clusters identify areas for targeted surveillance and livestock vaccination, while the seasonal case data suggest prioritizing vaccination campaigns for February or early March ahead of the April peak. A regional approach for studying the role of livestock trading between Son La and neighbouring provinces in anthrax occurrence is recommended., (© 2024 The Authors. Zoonoses and Public Health published by Wiley‐VCH GmbH.)

Anthrax is a zoonotic disease caused by a spore-forming gram-positive bacterium, Bacillus anthracis. Increased anthropogenic factors inside wildlife-protected areas may worsen the spillover of the disease at the interface. Consequently, environmental suitability prediction for B. anthracis spore survival to locate a high-risk area is urgent. Here, we identified a potentially suitable habitat and a high-risk area for appropriate control measures. Our result revealed that a relatively largest segment of Omo National Park, about 23.7% (1,218 square kilometers) of the total area; 36.6% (711 square kilometers) of Mago National Park, and 29.4% (489 square kilometers) of Tama wildlife Reserve predicted as a high-risk area for the anthrax occurrence in the current situation. Therefore, the findings of this study provide the priority area to focus on and allocate resources for effective surveillance, prevention, and control of anthrax before it causes devastating effects on wildlife., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Anthrax and brucellosis are endemic national priority zoonotic diseases in Ethiopia. This study assess the possible factors explaining the current limited information available on animal and human cases in pastoral communities., Methods: Two questionnaire surveys gathered data from 509 pastoralists and 51 healthcare providers between February and April 2019 in five districts of Afar and the Somali region (SRS)., Results: Among the 51 healthcare providers, 25 (49%) and 38 (74.5%) had heard of brucellosis, and anthrax, respectively. Of those, only 3 (12%) and 14 (36.8%) knew the symptoms of brucellosis and Anthrax. None of the Health Extension Workers knew any disease symptoms. Healthcare providers recalled two human cases of brucellosis and 39 cases of Anthrax in the last 12 months, based on symptom-based diagnosis. Pastoralists had a moderate level of knowledge about diseases in their animals, with over half (52.4%; n = 267/509) understanding that animals can transmit diseases to people. Overall, 280 out of 508 (55.1%) and 333 out of 507 (65.7%) pastoralists had heard of brucellosis and Anthrax, respectively. Among the latter, 282 (51.3%) knew at least one preventive measure for Anthrax. However, disease knowledge among women was poor. Despite their knowledge, pastoralists engaged in risky unprotected animal handling, animal product consumption/usage as well as husbandry behaviors exposing them to pathogens and favoring the spread of diseases. They identified Anthrax as the most important zoonosis (47.6%) and as one of top three diseases suspected to cause mortality in their livestock. Pastoralists highlighted lack of vaccine coverage, availability and their timely administration. Both, pastoralists and healthcare providers stated the lack of disease awareness and the unavailability of drugs in the market as important challenges. Health facilities lacked protocols and standard operating procedures for managing zoonotic diseases, and did not have access to laboratory confirmation of pathogens., Conclusion: Our study revealed significant under-reporting of Anthrax and brucellosis, and weak prevention and response in humans, mostly associated with poor disease knowledge of healthcare providers. Ability to respond to animal outbreaks was limited by vaccine and drugs availability, timely vaccine administration and the mobility of pastoralists., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Tschopp, Kidanu. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Protective antigen (PA) is a protein produced by Bacillus anthracis. It forms part of the anthrax toxin and is a key immunogen in US and UK anthrax vaccines. In this study, we have conducted experiments to quantify PA in the supernatants of cultures of B. anthracis Sterne strain, which is the strain used in the manufacture of the UK anthrax vaccine. Then, for the first time, we quantify PA production and degradation via mathematical modelling and Bayesian statistical techniques, making use of this new experimental data as well as two other independent published data sets. We propose a single mathematical model, in terms of delay differential equations (DDEs), which can explain the in vitro dynamics of all three data sets. Since we did not heat activate the B. anthracis spores prior to inoculation, germination occurred much slower in our experiments, allowing us to calibrate two additional parameters with respect to the other data sets. Our model is able to distinguish between natural PA decay and that triggered by bacteria via proteases. There is promising consistency between the different independent data sets for most of the parameter estimates. The quantitative characterisation of B. anthracis PA production and degradation obtained here will contribute towards the ambition to include a realistic description of toxin dynamics, the host immune response, and anti-toxin treatments in future mechanistic models of anthrax infection., (© 2024. The Author(s).)

Context: The Centers for Disease Control and Prevention (CDC) and the US Postal Service (USPS) consider anthrax to be a potential threat to USPS workers. A county health department-owned pharmacy supports local USPS response in the event of an exposure. The pharmacy team identified the need to review and update the local anthrax response plan., Program/policy: A Pharmacy Point-of-Dispensing Toolkit and response plan for initial 10-day post-exposure antibiotic prophylaxis was developed for use by a local health department in the event of a mass anthrax exposure at a US Post Office sorting facility. The pharmacist's role in medical countermeasures planning for anthrax exposure is also discussed to illustrate how pharmacists' medication expertise can be utilized., Evaluation: The CDC's Public Health Preparedness Capabilities: National Standards for State and Local Planning framework and inputs from an interprofessional stakeholder team were used to develop a Medical Countermeasures Response Plan and Implementation Toolkit for mass point-of-dispensing (POD) in the event of an anthrax exposure., Implementation and Dissemination: Stakeholders attended a USPS Community Partner Training event where additional revisions to the toolkit were made. The toolkit and standing order are now implemented at the local health department to be reviewed and updated on a yearly basis by health department leadership., Discussion: Pharmacists can use their medication expertise and experience with patient education to design emergency response plans focused on increasing patient safety and medication adherence. Pharmacists should be involved in emergency response and medical countermeasures planning that involve medications., Competing Interests: The authors declare no conflicts of interest. Authors Joni Carroll, Kelsey Hake, Thai Nguyen, Amanda Rice, and Sarah Schneider are contract pharmacists with the Allegheny County Health Department Pharmacy at the time of article publication., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Improved methods are needed to prevent wildlife deaths from anthrax. Caused by Bacillus anthracis , naturally occurring outbreaks of anthrax are frequent but unpredictable. The commercially available veterinary vaccine is labeled for subcutaneous injection and is impractical for large-scale wildlife vaccination programs; therefore, oral vaccination is the most realistic method to control and prevent these outbreaks. We reported the induction of an anthrax-specific lethal toxin (LeTx) neutralizing antibody response in mice following oral vaccination with alginate microcapsules containing B. anthracis Sterne strain 34F2 spores, coated with poly-L-lysine (PLL) and vitelline protein B (VpB). We continued evaluating our novel vaccine formulation through this proof-of-concept study in white-tailed deer (WTD; Odocoileus virginianus ; n = 9). We orally vaccinated WTD via needle-free syringe with three formulations of the encapsulated vaccine: 1) PLL-VpB-coated microcapsules with 10 7-8 spores/ml ( n = 5), 2) PLL-VpB-coated microcapsules with 10 9-10 spores/ml ( n = 2), and 3) PLL-coated microcapsules with 10 9-10 spores/ml ( n = 2). Although the limited sample sizes require continued experimentation, we observed an anthrax-specific antibody response in WTD serum following oral vaccination with PLL-coated microcapsules containing 10 9 spores/ ml. Furthermore, this antibody response neutralized anthrax LeTx in vitro, suggesting that continued development of this vaccine may allow for realistic wildlife anthrax vaccination programs.

Background: Anthrax is a non-contagious zoonotic disease caused by the Gram-positive, spore-forming bacterium Bacillus anthracis. Infection is common in livestock and wild animals such as cattle, goats, sheep, camels, and antelopes. In humans, anthrax may occur after contact with contaminated carcasses or animal products like milk and meat. The best method to prevent anthrax in people is to ensure livestock are vaccinated, which significantly limits the risk of zoonotic spread to humans. However, the rate of vaccination of domesticated animals kept by nomadic pastoralists in West Africa is low. These groups regularly cross over national boundaries with their grazing herds. Nigeria is a country that historically has done comparatively well to contain this public health threat. However, in 2023 several outbreaks of human disease appear linked to the consumption of anthrax-contaminated animal products brought into Nigeria by pastoralists from neighboring countries. Clinical manifestations include skin sores or ulcers, nausea, vomiting, and fever. This article aims to raise awareness of recent outbreaks of anthrax in West Africa and to call for a renewed focus on measures to combat this neglected public health concern to the region., Main Body: The imperative to pinpoint pivotal issues relating to the ongoing emergence of anthrax cases in Nigeria cannot be overstated. By delving into the prevalence of anthrax in both livestock and human populations residing along Nigeria's borders, unraveling the genetic diversity and potential sources of B. anthracis strains, and identifying the primary animal host(s) responsible for transmission, we stand to enhance our understanding of this critical issue. Furthermore, investigating the multifaceted factors contributing to anthrax transmission, assessing community knowledge and practices, mapping common migratory routes of pastoralists, and formulating targeted intervention strategies tailored to the challenges of border communities, are each crucial steps towards effective control and prevention., Conclusion: Closing these knowledge gaps on anthrax is not only essential for safeguarding both animal and human health but also for fostering sustainable and resilient communities. Addressing research questions on these interdisciplinary concerns will undoubtedly pave the way for informed decision-making, proactive measures, and a more secure future for Nigeria and its border regions., (© 2024. The Author(s).)

Anthrax Immune Globulin Intravenous (AIGIV [ANTHRASIL]), was developed for the treatment of toxemia associated with inhalational anthrax. It is a plasma product collected from individuals vaccinated with anthrax vaccine and contains antitoxin IgG antibodies against Bacillus anthracis protective antigen. A pharmacokinetic (PK) and exposure-response model was constructed to assess the PKs of AIGIV in anthrax-free and anthrax-exposed rabbits, non-human primates and anthrax-free humans, as well as the relationship between AIGIV exposure and survival from anthrax, based on available preclinical/clinical studies. The potential effect of anthrax on the PKs of AIGIV was evaluated and estimates of survival odds following administration of AIGIV protective doses with and without antibiotic co-treatment were established. As the developed PK model can simulate exposure of AIGIV in any species for any dosing scenario, the relationship between the predicted area under the concentration curve of AIGIV in humans and the probability of survival observed in preclinical studies was explored. Based on the simulation results, the intravenous administration of 420 U (units of potency as measured by validated Toxin Neutralization Assay) of AIGIV is expected to result in a > 80% probability of survival in more than 90% of the human population. Additional simulations suggest that exposure levels were similar in healthy and obese humans, and exposure in pediatrics is expected to be up to approximately seven-fold higher than in healthy adults, allowing for doses in pediatric populations that ranged from one to seven vials. Overall, the optimal human dose was justified based on the PK/pharmacodynamic (PD) properties of AIGIV in animals and model-based translation of PK/PD to predict human exposure and efficacy., (© 2023 Emergent Biosolutions. Clinical Pharmacology & Therapeutics © 2023 American Society for Clinical Pharmacology and Therapeutics.)

Outbreaks of anthrax, caused by the soilborne bacterium Bacillus anthracis, are a continuous threat to free-ranging livestock and wildlife in enzootic regions of the United States, sometimes causing mass mortalities. Injectable anthrax vaccines are commercially available for use in livestock, and although hand injection is not a cost- or time-effective long-term management plan for prevention in wildlife, it may provide a tool for managers to target selectively animals of high conservation or economic value. Vaccine-induced anthrax-specific antibody responses have been reported previously in white-tailed deer (Odocoileus virginianus), but the protective nature was not determined. In this study, five white-tailed deer were subcutaneously vaccinated with one dose (1 mL) of the Anthrax Spore Vaccine. Eight blood collections by jugular venipuncture were conducted over 146 d to measure the anthrax-specific antibody response in each deer's serum over time. Antibodies were first detected by ELISA and later with toxin neutralization assays to estimate in vitro protection. Average peak absorbance by ELISA occurred at 14 d postvaccination, whereas average peak in vitro protection occurred at 28 d postvaccination. Observed in vitro protection on average for white-tailed deer after this single-dose vaccination protocol lasted 42-56 d postvaccination, although three individuals still maintained lethal toxin-neutralizing serum antibody titers out to 112 d postvaccination. Vaccination responses were variable but effective to some degree in all white-tailed deer., (© Wildlife Disease Association 2024.)

Anthrax is reported globally with varying disease intensity and seasonality among countries. In Vietnam, anthrax epidemiology and ecology remain understudied. We used historical data of human and livestock anthrax from 2004 to 2021 in Lai Chau province, to identify spatial clusters of human and livestock anthrax, describe epidemiological characteristics, and compare livestock anthrax vaccine coverage to human and livestock disease incidence. Local Moran's I (LISA) using spatial Bayes smoothed commune-level cumulative incidence (per 10,000) for the study period, epidemiological descriptive statistics, livestock vaccine coverage data, and annual incidence rates (per 10,000) at provincial level were used. LISA identified a human anthrax hotspot (high-high) in the southeast which did not overlap spatially with livestock anthrax hotspots in southeastern and northeastern communes. Most human cases were male, aged 15-59 years, handled sick animals, and/or consumed contaminated meat. Almost all cases were reported by grassroot health facilities with a delay of 6.3 days between exposure and case notification to the national surveillance system. 80 % of human cases were reported from June-October. The increase in disease incidence occurred shortly after livestock anthrax vaccine coverage decreased. This study informs vaccination strategy and targeted surveillance and control measures in newly identified high-risk areas and seasons of anthrax., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Pulmonary anthrax caused by exposure to inhaled Bacillus anthracis , the most lethal form of anthrax disease, is a continued military and public health concern for the United States. The vaccine AV7909, consisting of the licensed anthrax drug substance AVA adjuvanted with CpG7909, induces high levels of toxin neutralizing antibodies in healthy adults using fewer doses than AVA. This study compares the ability of one- or two-dose regimens of AV7909 to induce a protective immune response in guinea pigs challenged with a lethal dose of aerosolized B. anthracis spores 6 weeks after the last vaccine dose. The results indicated that AV7909 was less effective when delivered as a single dose compared to the two-dose regimen that resulted in dose-dependent protection against death. The toxin neutralizing assay (TNA) titer and anti-PA IgG responses were proportional to the protective efficacy, with a 50% TNA neutralizing factor (NF 50 ) greater than 0.1 associated with survival in animals receiving two doses of vaccine. The strong protection at relatively low TNA NF 50 titers in this guinea pig model supports the exploration of lower doses in clinical trials to determine if these protective levels of neutralizing antibodies can be achieved in humans; however, protection with a single dose may not be feasible.

Anthrax is more prevalent in impoverished nations and those without veterinarian public health initiatives. A comprehensive strategy was pursued to build an anthrax-free model in which there would be no anthrax. The strategy included routine vaccination, increased public awareness, rapid confirmation, and prompt disposal, as well as the establishment of an effective surveillance system, the development of an emergency prevention system, the enforcement of regulations, and the improvement of collaboration between human health and veterinary services. From 2017 through 2020, several initiatives including both social and laboratory activities were performed. After strictly applying the study's procedures, it was determined that the vast majority of community people (97.5%) were knowledgeable of the disease's nature, prevalence, significance to public health, and treatment in the study area. The farmers' risky practices and attitudes about the killing of sick livestock decreased dramatically (85%). The vaccination rate climbed from 40% to 85%, and the proportion of farmers who can presumptively identify anthrax based on its prominent clinical symptoms rose from 30% to 85%. A confirmation methodology based on PCR was implemented. A geographical map depicting the green and dangerous pastureland was created. The formation of a steering group to assess the progress of scientific activity. Locals established a slaughterhouse in that location, where individuals slaughtered their animals following veterinary examination and strictly followed drug withdrawal period. The contaminated area has been free of anthrax infection for four years as a consequence of these efforts. There also reduction of antibiotic used due to mass awareness. The study indicated that the model is an efficient, effective, and appropriate technique for establishing an anthrax-free zone where no anthrax outbreaks would occur. It could be replicated in any part of the world where socioeconomic and geographical conditions are similar., Competing Interests: Declaration of Competing Interest I confirm that this work is original and has not been published elsewhere, nor is it currently under consideration for publication elsewhere. In this paper, we report this integrated model that could be use in any developing countries for control of anthrax disease both in human and livestock. We believe that this manuscript is appropriate for publication by Journal of Infection and Public Health as it address the concept of One Health, also it will provide initial thought for future researchers, policy maker to control anthrax disease from any contaminated area by using this model. Here also declared that all authors have seen and approved the content of the manuscript and have contributed significantly to the work. We have no conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pulmonary anthrax is the most fatal clinical form of anthrax and currently available injectable vaccines do not provide adequate protection against it. Hence, next-generation vaccines that effectively induce immunity against pulmonary anthrax are urgently needed. In the present study, we prepared an attenuated and low protease activity Bacillus anthracis strain A16R-5.1 by deleting five of its extracellular protease activity-associated genes and its lef gene through the CRISPR-Cas9 genome editing system. This mutant strain was then used to formulate a lethal toxin (LeTx)-free culture supernatant extract (CSE) anthrax vaccine, of which half was protective antigen (PA). We generated liquid, powder, and powder reconstituted formulations that could be delivered by aerosolized intratracheal inoculation. All of them induced strong humoral, cellular, and mucosal immune responses. The vaccines also produced LeTx neutralizing antibodies and conferred full protection against the lethal aerosol challenges of B. anthracis Pasteur II spores in mice. Compared to the recombinant PA vaccine, the CSE anthrax vaccine with equal PA content provided superior immunoprotection against pulmonary anthrax. The preceding results suggest that the CSE anthrax vaccine developed herein is suitable and scalable for use in inhalational immunization against pulmonary anthrax.

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., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. CDC and contributors to this work disclose that they have no financial interests or other relationships with the manufacturers of commercial products, suppliers of commercial services, or commercial supporters that would unfairly influence these CDC recommendations with the following exceptions: Arthur Friedlander reports funding from the U.S. Department of Defense Threat Reduction Agency for research on anthrax vaccines and therapeutics. However, none of the vaccines or therapeutics were discussed for inclusion in the guidelines. Adolf W. Karchmer receives an honorarium for service on the data and safety monitoring board (tofacitinib) for Pfizer. Todd Semla’s spouse owns stock in Abbott. Both Pfizer and Abbott manufacture antimicrobial drugs included in the guidelines. No other potential conflicts of interest were disclosed.

Introduction: The virulence binding factor, protective antigen (pag) and poly-D-γ-glutamate capsular (cap) genes, peculiar to Bacillus anthracis are located in the pXO1 and pXO2 plasmids which are transferable horizontally to related species called "cereus group". The cereus group are usually isolated from the environmental/food samples and have been implicated in debilitating human and animal anthrax-like diseases. This study was designed to investigate the presence of the anthrax virulence genes in different Bacillus spp. isolated from handwashing facilities during COVID-19 pandemic in Lagos, Nigeria., Methodology: The Bacillus anthracis (OK316847), B. thuringiensis (OK316855), B. amyloliquefaciens (OK316857), B. cereus (OK316858) and B. thuringiensis (OK316859) previously isolated from rinsates and bowl water in two local government areas (LGAs) of Lagos state were further investigated by the polymerase chain reaction (PCR) amplification of the pag and cap genes using specific primers., Results: Bacillus anthracis and B. cereus co-harboured the two 578 bp cap and 364 bp pag genes while B. thuringiensis only harboured the cap gene. Similarly, the non-cereus B. amyloliquefaciens was found to habour the pag gene., Conclusions: The two anthrax toxin genes were amplified in the Bacillus spp isolated from rinsates and bowl water used in hand washing in the two study LGAs. Given that these virulence genes have a global consequence and are a potential threat to life, this study calls for an extensive surveillance, and reassessment of gene regulators and plasmid distribution among these strains in our environment., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Tajudeen A Bamidele, Bamidele T Odumosu, Princess T Adenola, James Ameh, Olaide K Kareem, Babatunde Osoba, Oliver C Ezechi, Babatunde L Salako.)

Introduction: Nuclear reactor incidents and bioterrorism outbreaks are concerning public health disasters. Little is known about US Food and Drug Administration (FDA)-approved agents that can mitigate consequences of these events. We review FDA data supporting regulatory approvals of these agents., Areas Covered: We reviewed pharmaceutical products approved to treat Hematopoietic Acute Radiation Syndrome (H-ARS) and to treat or prevent pulmonary infections following Bacillus anthracis (anthrax) exposure. Four drugs were approved for H-ARS: granulocyte-colony stimulating factor (G-CSF), granulocyte/macrophage colony stimulating factor, pegylated G-CSF, and romiplostim. For bioterrorism-associated anthrax, the FDA approved five antibiotics (doxycycline, penicillin-G, levofloxacin, moxifloxacin, and ciprofloxacin), two monoclonal antibodies (obiltoxaximab and raxibacumab), one polyclonal antitoxin (Anthrax Immune Globulin Intravenous) and two vaccines (Anthrax Vaccine Adsorbed and Anthrax Vaccine Adsorbed with an adjuvant). A national stockpile system ensures that communities have ready access to these agents. Our literature search was based on data included in drugs@FDA (2001-2023)., Expert Opinion: Two potential mass public health disasters are aerosolized anthrax dissemination and radiological incidents. Five agents authorized for anthrax emergencies only have FDA approval for this indication, five antibiotics have FDA approvals as antibiotics for common infections and for bacillus anthrax, and four agents have regulatory approvals for supportive care for cancer and for radiological incidents.

A recombinant protective antigen anthrax vaccine (GC1109) is being developed as a new-generation vaccine by the Korea Disease Control and Prevention Agency. In accordance with the ongoing step 2 of phase II clinical trials, the immunogenicity and protective efficacy of the booster dose of GC1109 were evaluated in A/J mice after 3 serial vaccinations at 4-week intervals. The results indicated that the booster dose significantly increased the production of anti-protective antigen (PA) IgG and toxin-neutralizing antibody (TNA) compared with those of the group without booster. An enhanced protective effect of the booster dose was not observed because the TNA titers of the group without booster were high enough to confer protection against spore challenge. Additionally, the correlation between TNA titers and probability of survival was determined for calculating the threshold TNA titer levels associated with protection. The threshold 50 % neutralization factor (NF 50 ) of TNA showing 70 % probability of protection was 0.21 in A/J mice with 1,200 LD 50 Sterne spores challenge. These results indicate that GC1109 is a promising candidate as a new-generation anthrax vaccine and that a booster dose might provide enhanced protection by producing toxin-neutralizing antibodies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Specific knowledge on the distribution of anthrax, a zoonosis caused by Bacillus anthracis , in Southeast Asia, including Vietnam, remains limited. In this study, we describe disease incidence and spatial distribution of human and livestock anthrax using spatially smoothed cumulative incidence from 2004 to 2020 in Cao Bang province, Vietnam. We employed the zonal statistics routine a geographic information system (GIS) using QGIS, and spatial rate smoothing using spatial Bayes smoothing in GeoDa. Results showed higher incidence of livestock anthrax compared with human anthrax. We also identified co-occurrence of anthrax in humans and livestock in northwestern districts and the province center. Livestock anthrax vaccine coverage was <6% and not equally distributed among the districts of Cao Bang province. We provide implications for future studies and recommend improving disease surveillance and response through data sharing between human and animal health sectors.

Introduction: Bacillus anthracis is the causative agent for the lethal disease anthrax, primarily affecting animals and humans in close contact with an infected host. The pathogenicity of B. anthracis is attributed to the secreted exotoxins and their outer capsule. The host cell-binding exotoxin component "protective antigen" (PA) is reported to be a potent vaccine candidate. The aim of our study is to produce several PA constructs and analyze their vaccine potential., Methods: We have designed the various subunit, PA-based recombinant proteins, i.e., full-length Protective antigen (PA-FL), C-terminal 63 kDa fragment (PA63), Protective antigen domain 1-domain 4 chimeras (PA-D1-4) and protective antigen domain 4 (PA-D4) and analyzed their vaccine potential with different human-compatible adjuvants in the mouse model. We have optimized the process and successfully expressed our recombinant antigens as soluble proteins, except full-length PA. All the recombinant antigen formulations with three different adjuvants i.e., Addavax, Alhydrogel, and Montanide ISA 720, were immunized in different mouse groups. The vaccine efficacy of the formulations was analyzed by mouse serum antigen-specific antibody titer, toxin neutralization assay, and survival analysis of mouse groups challenged with a lethal dose of B. anthracis virulent spores., Results: We have demonstrated that the PA-FL addavax and PA63 addavax formulations were most effective in protecting spore-challenged mice and serum from the mice immunized with PAFL addavax, PA-FL alhydrogel, PA63 addavax, and PA63 alhydrogel formulations were equivalently efficient in neutralizing the anthrax lethal toxin. The higher levels of serum Th1, Th2, and Th17 cytokines in PA-FL addavax immunized mice correspond to the enhanced protection provided by the formulation in challenged mice., Discussion: We have demonstrated that the PA-FL addavax and PA63 addavax formulations exhibit equivalent efficiency as vaccine formulation both in a mouse model of anthrax and mammalian cell lines. However, PA63 is a smaller antigen than PA-FL and more importantly, PA63 is expressed as a soluble protein in E. coli, which imparts a translational advantage to PA63-based formulation. Thus, the outcome of our study has significant implications for the development of protective antigen-based vaccine formulations for human use against the lethal disease anthrax., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sharma, Bahl, Srivastava, Shamim, Bhatnagar and Gaur.)

This study aimed to determine optimal mitigation strategies in the event of an aerosolized attack with Bacillus anthracis , a category A bioterrorism agent with a case fatality rate of nearly 100% if inhaled and untreated. To simulate the effect of an anthrax attack, we used a plume dispersion model for Sydney, Australia, accounting for weather conditions. We determined the radius of exposure in different sizes of attack scenarios by spore quantity released per second. Estimations of different spore concentrations were then used to calculate the exposed population to inform a Susceptible-Exposed-Infected-Recovered (SEIR) deterministic mathematical model. Results are shown as estimates of the total number of exposed and infected people, along with the burden of disease, to quantify the amount of vaccination and antibiotics doses needed for stockpiles. For the worst-case scenario, over 500,000 people could be exposed and over 300,000 infected. The number of deaths depends closely on timing to start postexposure prophylaxis. Vaccination used as a postexposure prophylaxis in conjunction with antibiotics is the most effective mitigation strategy to reduce deaths after an aerosolized attack and is more effective when the response starts early (2 days after release) and has high adherence, while it makes only a small difference when started late (after 10 days).

Anthrax is a serious zoonosis caused by Bacillus anthracis, which primarily affects wild herbivorous animals with spillover into humans. The disease occurs nearly worldwide but is poorly reported in Southeast Asian countries. In Vietnam, anthrax is underreported, and little is known about its temporal and spatial distributions. This paper examines the spatio-temporal distribution and epidemiological characteristics of human and livestock anthrax from Dien Bien province, Vietnam from 2010 to 2019. We also aim to define the role of livestock vaccination in reducing human cases. Historical anthrax data were collected by local human and animal health sectors in the province. Spatial rate smoothing and spatial clustering analysis, using Local Moran's I in GeoDa and space-time scan statistic in SaTScan, were employed to address these objectives. We found temporal and spatial overlap of anthrax incidence in humans and livestock with hotspots of human anthrax in the east. We identified three significant space-time clusters of human anthrax persisting from 2010 to 2014 in the east and southeast, each with high relative risk. Most of the human cases were male (69%), aged 15-59 years (80%), involved in processing, slaughtering, or eating meat of sick or dead livestock (96.9%) but environmental and unknown exposure were reported. Animal reports were limited compared to humans and at coarser spatial scale, but in areas with human case clusters. In years when livestock vaccination was high (>~25%), human incidence was reduced, with the opposite effect when vaccine rates dropped. This indicates livestock vaccination campaigns reduce anthrax burden in both humans and livestock in Vietnam, though livestock surveillance needs immediate improvement. These findings suggest further investigation and measures to strengthen the surveillance of human and animal anthrax for other provinces of Vietnam, as well as in other countries with similar disease context., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Using data collected from previous (n = 86) and prospective (n = 132) anthrax outbreaks, we enhanced prior ecological niche models (ENM) and added kernel density estimation (KDE) approaches to identify anthrax hotspots in Kenya. Local indicators of spatial autocorrelation (LISA) identified clusters of administrative wards with a relatively high or low anthrax reporting rate to determine areas of greatest outbreak intensity. Subsequently, we modeled the impact of vaccinating livestock in the identified hotspots as a national control measure. Anthrax suitable areas included high agriculture zones concentrated in the western, southwestern and central highland regions, consisting of 1043 of 1450 administrative wards, covering 18.5% country landmass, and hosting 30% of the approximately 13 million cattle population in the country. Of these, 79 wards covering 5.5% landmass and hosting 9% of the cattle population fell in identified anthrax hotspots. The rest of the 407 administrative wards covering 81.5% of the country landmass, were classified as low anthrax risk areas and consisted of the expansive low agricultural arid and semi-arid regions of the country that hosted 70% of the cattle population, reared under the nomadic pastoralism. Modelling targeted annual vaccination of 90% cattle population in hotspot administrative wards reduced > 23,000 human exposures. These findings support an economically viable first phase of anthrax control program in low-income countries where the disease is endemic, that is focused on enhanced animal and human surveillance in burden hotspots, followed by rapid response to outbreaks anchored on public education, detection and treatment of infected humans, and ring vaccination of livestock. Subsequently, the global anthrax elimination program focused on sustained vaccination and surveillance in livestock in the remaining few hotspots for a prolonged period (> 10 years) may be implemented., (© 2022. The Author(s).)

Anthrax infections caused by Bacillus anthracis are an ongoing bioterrorism and livestock threat worldwide. Current approaches for management, including extended passive antibody transfusion, antibiotics, and prophylactic vaccination, are often cumbersome and associated with low patient compliance. Here, we report on the development of an adjuvanted nanotoxoid vaccine based on macrophage membrane-coated nanoparticles bound with anthrax toxins. This design leverages the natural binding interaction of protective antigen, a key anthrax toxin, with macrophages. In a murine model, a single low-dose vaccination with the nanotoxoids generates long-lasting immunity that protects against subsequent challenge with anthrax toxins. Overall, this work provides a new approach to address the ongoing threat of anthrax outbreaks and bioterrorism by taking advantage of an emerging biomimetic nanotechnology.

Anthrax is a priority zoonosis for control in Vietnam. The geographic distribution of anthrax remains to be defined, challenging our ability to target areas for control. We analyzed human anthrax cases in Vietnam to obtain anthrax incidence at the national and provincial level. Nationally, the trendline for cases remained at ≈61 cases/year throughout the 26 years of available data, indicating control efforts are not effectively reducing disease burden over time. Most anthrax cases occurred in the Northern Midlands and Mountainous regions, and the provinces of Lai Chau, Dien Bien, Lao Cai, Ha Giang, Cao Bang, and Son La experienced some of the highest incidence rates. Based on spatial Bayes smoothed maps, every region of Vietnam experienced human anthrax cases during the study period. Clarifying the distribution of anthrax in Vietnam will enable us to better identify risk areas for improved surveillance, rapid clinical care, and livestock vaccination campaigns.

Background: Sufficient and diverse medical countermeasures against severe pathogenic infections, such as inhalation anthrax, are a critical need. Azithromycin and clarithromycin are antimicrobials commonly used for both upper and lower respiratory infections. They inhibit protein synthesis by blocking the formation of the 50S ribosomal subunit. To expand the armamentarium, these 2 antibiotics were evaluated in a postexposure prophylactic model of inhalation anthrax in cynomolgus macaques., Methods: This prophylaxis study had 4 test arms: azithromycin, clarithromycin, a levofloxacin control, and a placebo. Beginning 24 hours after exposure to a target challenge dose of 200 lethal dose 50 (LD50) of Bacillus anthracis Ames spores, animals were treated orally until 30 days postchallenge and then observed until 75 days postchallenge., Results: The test group that received clarithromycin had a survival rate of 67%. The test group that received azithromycin had a survival rate of 50%, but the peak azithromycin plasma levels achieved were <30 ng/mL-much lower than the expected 410 ng/mL. The levofloxacin positive control had a survival rate of 50%; all of the negative controls succumbed to infection., Conclusions: The efficacy of clarithromycin prophylaxis was statistically significant compared with placebo, while azithromycin prophylaxis was indistinguishable from placebo. Given the low plasma concentrations of azithromycin achieved in the study, it is not surprising that half the animals succumbed to anthrax during the dosing period; the animals that survived beyond the time during which placebo control animals succumbed survived to the end of the observation period., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: The deliberate use of Bacillus anthracis spores is believed by the US government to be a high bioweapons threat. The first line of defense following potential exposure to B. anthracis spores would be postexposure prophylaxis with antimicrobials that have activity against B. anthracis. Additional therapies to address the effects of toxins may be needed in systemically ill individuals. Over the last 2 decades, the United States government (USG) collaborated with the private sector to develop, test, and stockpile 3 antitoxins: anthrax immunoglobulin intravenous (AIGIV), raxibacumab, and obiltoxaximab. All 3 products target protective antigen, a protein factor common to the 2 exotoxins released by B. anthracis, and hamper or block the toxins' effects and prevent or reduce pathogenesis. These antitoxins were approved for licensure by the United States Food and Drug Administration based on animal efficacy studies compared to placebo., Methods: We describe USG-sponsored pre- and postlicensure studies that compared efficacy of 3 antitoxins in a New Zealand White rabbit model of inhalation anthrax; survival following a lethal aerosolized dose of B. anthracis spores was the key measure of effectiveness. To model therapeutic intervention, intravenous treatments were started following onset of antigenemia., Results: In pre- and postlicensure studies, all 3 antitoxins were superior to placebo; in the postlicensure study, raxibacumab and obiltoxaximab were superior to AIGIV, but neither was superior to the other., Conclusions: These data illustrate the relative therapeutic benefit of the 3 antitoxins and provide a rationale to prioritize their deployment., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies., Methods: We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans., Results: We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, β-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx., Conclusions: These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Background: Bacillus anthracis, the causative agent for anthrax, poses a potential bioterrorism threat and is capable of causing mass morbidity and mortality. Antimicrobials are the mainstay of postexposure prophylaxis (PEP) and treatment of anthrax. We conducted this safety review of 24 select antimicrobials to identify any new or emerging serious or severe adverse events (AEs) to help inform their risk-benefit evaluation for anthrax., Methods: Twenty-four antimicrobials were included in this review. Tertiary data sources (e.g. Lactmed, Micromedex, REPROTOX) were reviewed for safety information and summarized to evaluate the known risks of these antimicrobials. PubMed was also searched for published safety information on serious or severe AEs with these antimicrobials; AEs that met inclusion criteria were abstracted and reviewed., Results: A total of 1316 articles were reviewed. No consistent observations or patterns were observed among the abstracted AEs for a given antimicrobial; therefore, the literature review did not reveal evidence of new or emerging AEs that would add to the risk-benefit profiles already known from tertiary data sources., Conclusions: The reviewed antimicrobials have known and/or potential serious or severe risks that may influence selection when recommending an antimicrobial for PEP or treatment of anthrax. Given the high fatality rate of anthrax, the risk-benefit evaluation favors use of these antimicrobials for anthrax. The potential risks of antimicrobials should not preclude these reviewed antimicrobials from clinical consideration for anthrax but rather guide appropriate antimicrobial selection and prioritization across different patient populations with risk mitigation measures as warranted., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Bacillus anthracis is a high-priority threat agent because of its widespread availability, easy dissemination, and ability to cause substantial morbidity and mortality. Although timely and appropriate antimicrobial therapy can reduce morbidity and mortality, the role of adjunctive therapies continues to be explored., Methods: We searched 11 databases for articles that report use of anthrax antitoxins in treatment or prevention of systemic anthrax disease published through July 2019. We identified other data sources through reference search and communication with experts. We included English-language studies on antitoxin products with approval by the US Food and Drug Administration (FDA) for anthrax in humans, nonhuman primates, and rabbits. Two researchers independently reviewed studies for inclusion and abstracted relevant data., Results: We abstracted data from 12 publications and 2 case reports. All 3 FDA-approved anthrax antitoxins demonstrated significant improvement in survival as monotherapy over placebo in rabbits and nonhuman primates. No study found significant improvement in survival with combination antitoxin and antimicrobial therapy compared to antimicrobial monotherapy. Case reports and case series described 25 patients with systemic anthrax disease treated with antitoxins; 17 survived. Animal studies that used antitoxin monotherapy as postexposure prophylaxis (PEP) demonstrated significant improvement in survival over placebo, with greatest improvements coming with early administration., Conclusions: Limited human and animal evidence indicates that adjunctive antitoxin treatment may improve survival from systemic anthrax infection. Antitoxins may also provide an alternative therapy to antimicrobials for treatment or PEP during an intentional anthrax incident that could involve a multidrug-resistant B. anthracis strain., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

We undertook a Phase 4 clinical trial to assess the effect of time interval between booster doses on serological responses to AVP. The primary objective was to evaluate responses to a single booster dose in two groups of healthy adults who had previously received a complete 4-dose primary course. Group A had received doses on schedule while Group B had not had one for ≥2 years. Secondary objectives were to evaluate the safety and tolerability of AVP booster doses, and to gain information on correlates of protection to aid future anthrax vaccine development. Blood samples were taken on Day 1 before dosing, and on Days 8, 15, 29 and 120, to measure Toxin Neutralisation Assay (TNA) NF 50 values and concentrations of IgG antibodies against Protective Antigen (PA), Lethal Factor (LF) and Edema Factor (EF) by ELISA. For each serological parameter, fold changes from baseline following the trial AVP dose were greater in Group B than Group A at every time-point studied. Peak responses correlated positively with time since last AVP dose (highest values being observed after intervals of ≥10 years), and negatively with number of previous doses (highest values occurring in individuals who had received a primary course only). In 2017, having reviewed these results, the Joint Committee on Vaccination and Immunisation (JCVI) updated UK anthrax vaccination guidelines, extending the interval between routine AVP boosters from one to 10 years. Booster doses of AVP induce significant IgG responses against the three anthrax toxin components, particularly PA and LF. Similarly high responses were observed in TNA, a recognised surrogate for anthrax vaccine efficacy. Analysis of the 596 TNA results showed that anti-PA and anti-LF IgG make substantial independent contributions to neutralisation of anthrax lethal toxin. AVP may therefore have advantages over anthrax vaccines that depend on generating immunity to PA alone., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Objective: To analyze the epidemiological characteristics of anthrax in China from 2017 to 2019 and molecular typing of Bacillus anthracis isolated from some provinces (autonomous regions). Methods: Surveillance data of anthrax cases reported from 2017 to 2019 in the Infectious Disease Surveillance information System of China Disease Prevention and Control and the Public Health Emergency Reporting and Management Information System were collected, and descriptive epidemiological methods were used to analyze the epidemic characteristics, including the temporal, geographic and demographic distribution of this disease. A total of 47 strains of Bacillus anthracis isolated from 2017 to 2019 were analyzed by canSNP and MLVA15. Results: A total of 951 cases of anthrax were reported from 2017 to 2019, of which 938 were cutaneous anthrax, representing 98.63% of the total number reported. It was mainly distributed in the west and northeast of China, and the three provinces with the highest number of cases were Gansu (215), Sichuan (202) and Qinghai (191). Cases had been reported throughout the year, more cases occurred in the summer and autumn, and August was the month with the most cases,66.35% (211/318), 72.32% (243/336) and 68.01% (202/297) of cases were reported during June to September. The age distribution was mainly between 20 and 59 years old, accounting for more than 80% of all cases. The number of male cases was significantly higher than that of female cases, the ratio of male to female was about 3∶1. The occupations were mainly herdsmen and farmers, accounting for 49.70% to 58.18% and 31.45% to 36.70%, respectively. Public health events occurred every year, and 29 events had been reported from 2017 to 2019. canSNP analysis showed that 37 of the 47 strains belonged to the A.Br.001/002 subgroup and 10 belonged to the A.Br.Ames subgroup. MLVA15 analysis showed that there were 17 genotypes, of which 10 genotypes contained only one strain. Conclusion: Cutaneous anthrax was the predominant clinical type in China from 2017 to 2019.The seasonal, geographic and demographic distribution characteristics were evident.Molecular typing methods such as canSNP and MLVA15 can be used to trace the source of infectious diseases and provide technical support for anthrax prevention and control.

Anthrax is a serious infectious disease caused by Bacillus anthracis, rod-shaped gram-positive bacteria. The disease infects both humans and animals and causes severe illness.  Many vaccines have been developed for anthrax, but the vaccine with very high efficacy is yet to be developed. To overcome the problems of efficacy posed by the existing vaccines, a recombinant chimeric fusion protein containing domain 1 of lethal factor (LFD1) and domain 4 of Bacillus anthracis protective antigen (PA4) was used as antigen in copolymeric nanocapsules (NCs). Accordingly, the solvent evaporation double emulsion method was used to produce NCs containing recombinant chimeric fusion protein (LFD1-PA4). Zeta sizer and potential of nanoparticles, nanoparticle loading efficiency, release pattern of recombinant protein, and the possible effect of polylactic acid-polyethylene glycol (PLA-PEG) nanoparticle production method were investigated. Mice were used to test and evaluate the immune response. The mean titer of antibody produced against loaded LFD1-PA4 compared to free form showed a significant difference. The difference in antibody titer between the groups of once injected, twice injected, and free antigen was significant, and the highest antibody titer was found in the mice twice injected. In addition, a single-time loaded injection showed significantly higher antibodies than the free form injection indicating that loaded LFD1-PA4 into PLA-PEG nanoparticles elicits a stronger immune response. This study showed that LFD1-PA4 fusion protein from Bacillus anthracis served as an active antigen in mice. Also, the nanocarrier (PLA-PEG) containing the antigen can stimulate the immune system in the mice, owing to their controlled release property.

Background: The potential use of Bacillus anthracis as a bioterrorism weapon requires a safe and effective vaccine that can be immediately distributed for mass vaccination. Protective antigen (PA), a principal component of virulence factors edema toxin and lethal toxin of B. anthracis, has been the topic of extensive research. Previously, full-length PA (PA83) was manufactured using a transient plant-based expression system. Immunization with this PA83 antigen formulated with Alhydrogel® adjuvant elicited strong neutralizing immune responses in mice and rabbits and protected 100% of rabbits from a lethal aerosolized B. anthracis challenge. This Phase 1 study evaluates this vaccine's safety and immunogenicity in healthy human volunteers., Methods: This first-in-human, single-blind, Phase 1 study was performed at a single center to investigate the safety, reactogenicity, and immunogenicity of the plant-derived PA83-FhCMB vaccine at four escalating dose levels (12.5, 25, 50 or 100 µg) with Alhydrogel® in healthy adults 18-49 years of age (inclusive). Recipients received three doses of vaccine intramuscularly at 28-day intervals. Safety was evaluated on days 3, 7, and 14 following vaccination. Immunogenicity was assessed using an enzyme-linked immunosorbent assay (ELISA) and a toxin neutralizing antibody (TNA) assay on days 0, 14, 28, 56, 84, and 180., Results: All four-dose ranges were safe and immunogenic, with no related serious adverse events observed. Peak ELISA Geometric Mean Concentration (GMC) and TNA ED 50 Geometric Mean Titer (GMT) were noted at Day 84, 1 month after the final dose, with the most robust response detected in the highest dose group. Antibody responses decreased by Day 180 across all dose groups. Long-term immunogenicity data beyond six months was not collected., Conclusions: This is the first study demonstrating a plant-derived subunit anthrax vaccine's safety and immunogenicity in healthy adults. The results support further clinical investigation of the PA83-FhCMB vaccine. ClinicalTrials.gov identifier. NCT02239172., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The potential use of biological agents has become a major public health concern worldwide. According to the CDC classification, Bacillus anthracis and Clostridium botulinum, the bacterial pathogens that cause anthrax and botulism, respectively, are considered to be the most dangerous potential biological agents. Currently, there is no licensed vaccine that is well suited for mass immunization in the event of an anthrax or botulism epidemic. In the present study, we developed a dual-expression system-based multipathogen DNA vaccine that encodes the PA-D4 gene of B. anthracis and the HCt gene of C. botulinum. When the multipathogen DNA vaccine was administered to mice and guinea pigs, high level antibody responses were elicited against both PA-D4 and HCt. Analysis of the serum IgG subtype implied a combined Th1/Th2 response to both antigens, but one that was Th2 skewed. In addition, immunization with the multipathogen DNA vaccine induced effective neutralizing antibody activity against both PA-D4 and HCt. Finally, the protection efficiency of the multipathogen DNA vaccine was determined by sequential challenge with 10 LD 50 of B. anthracis spores and 10 LD 50 of botulinum toxin, or vice versa, and the multipathogen DNA vaccine provided higher than 50% protection against lethal challenge with both high-risk biothreat agents. Our studies suggest the strategy used for this anthrax-botulinum multipathogen DNA vaccine as a prospective approach for developing emergency vaccines that can be immediately distributed on a massive scale in response to a biothreat emergency or infectious disease outbreak. Key points • A novel multipathogen DNA vaccine was constructed against anthrax and botulism. • Robust immune responses were induced following vaccination. • Suggests a potential vaccine development strategy against biothreat agents., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Anthrax caused by Bacillus anthracis is a fatal zoonotic disease with a high lethality and poor prognosis. Inhalational anthrax is the most severe of the three forms of anthrax. The currently licensed commercial human anthrax vaccines require a complex immunization procedure for efficacy and have side effects that limit its use in emergent situations. Thus, development of a better anthrax vaccine is necessary. In this study, we evaluate the potency and efficacy of aerosolized intratracheal (i.t.) inoculation with recombinant protective antigen (rPA) subunit vaccines against aerosolized B. anthracis Pasteur II spores (an attenuated strain) challenge in a B10.D2-Hc 0 mouse (deficient in complement component C5) model. Immunization of rPA in liquid, powder or powder reconstituted formulations via i.t. route conferred 100% protection against a 20× LD 50 aerosolized Pasteur II spore challenge in mice, compared with only 50% of subcutaneous (s.c.) injection with liquid rPA. Consistently, i.t. inoculation of rPA vaccines induced a higher lethal toxin (LeTx) neutralizing antibody titer, a stronger lung mucosal immune response and a greater cellular immune response than s.c. injection. Our results demonstrate that immunization with rPA dry powder vaccine via i.t. route may provide a stable and effective strategy to improve currently available anthrax vaccines and B10.D2-Hc 0 mice challenged with B. anthracis attenuated strains might be an alternative model for anthrax vaccine candidate screening., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.‬, (Copyright © 2022 Song, Zhang, Zhai, Guo, Zhao, Zhang, Hu, Xiong, Zhou, Lv and Yang.)

Background: This study is a baseline survey to assess the knowledge, attitude and practices with regards to the anthrax disease among the communities before demonstrating a One Health approach for elimination of human anthrax in an endemic district of Odisha. A total of 2670 respondents from 112 villages of 14 blocks were interviewed for the study using a structured questionnaire by multi-stage sampling method. Descriptive statistics were reported and logistic regression was performed to estimate the relationship between the variables and knowledge of anthrax., Result: Out of 2670 participants in the study, 76.25% were male and about half were illiterate. Most of the respondents (54.19%) were involved in agriculture as an occupation. 71% of the respondents had livestock in their houses and farming was the main purpose for keeping the livestock. Only one-fifth of the respondents (20.26%) knew about anthrax and a majority of them have come across the disease during community outbreaks. Almost 25.9% of livestock owners had knowledge about vaccination against anthrax disease although 83.4% of the livestock owners disposed the animal carcass by burial method., Conclusion: The study findings indicated that the community members had poor knowledge of cause, symptoms, transmission and prevention of anthrax disease which may be improved by a One Health approach., (© 2022. The Author(s).)

Live anthrax vaccine containing spores from attenuated strains STI-1 of Bacillus anthracis is used in Russia and former CIS (Commonwealth of Independent States) to prevent anthrax. In this paper we studied the duration of circulation of antibodies specific to spore antigens, the protective antigen (PA), the lethal factor (LF) and their domains (D) in donors' blood at different times after their immunization with live anthrax vaccine. The relationship between the toxin neutralization activity level and the level of antibodies to PA, LF and their domains was tested. The effect of age, gender and number of vaccinations on the level of adaptive post-vaccination immune response has been studied. It was shown that antibodies against PA-D1 circulate in the blood of donors for 1 year or more after immunization with live anthrax vaccine. Antibodies against all domains of LF and PA-D4 were detected in 11 months after vaccination. Antibodies against the spores were detected in 8 months after vaccination. A moderate positive correlation was found between the titers of antibodies to PA, LF, or their domains, and the TNA of the samples of blood serum from the donors., Competing Interests: The authors have declared that no competing interests exist.

Aims: Raxibacumab is a fully humanized monoclonal antibody that blocks the interaction of Bacillus anthracis toxins, thereby protecting target cells from its effects. Raxibacumab is approved in the USA for the treatment of adults and children with inhalational anthrax in combination with antibiotics, and for prophylaxis of inhalational anthrax. The aim of this investigation was to characterise the population pharmacokinetics and assess the effect of baseline demographic covariates on the disposition of raxibacumab., Methods: The data used for this analysis were obtained from 3 clinical trials and include 2229 blood samples from 322 healthy subjects who were randomised to receive a 40 mg/kg intravenous dose of raxibacumab over a period of 2.25 hours. Population pharmacokinetic modelling was performed using a nonlinear mixed effects approach. Secondary parameters of interest were the area under the curve, maximum concentration and the time of serum raxibacumab concentrations greater than or equimolar to the highest serum protective antigen concentrations observed for at least 28 days in any monkey challenged with B. anthracis that died., Results: Raxibacumab exposure in healthy subjects was described by a 2-compartment model. Interindividual variability was estimated for all model parameters, whilst residual variability was described by a proportional and additive error model. Weight was the only influential covariate with significant effect on disposition parameters., Conclusions: A dose of 40 mg/kg provided comparable exposure across the overall healthy subject population. Interindividual variability in raxibacumab vs. time profiles could partially be accounted for by differences in body weight., (© 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Aims: The US Food and Drug Administration's Animal Rule allows for the approval of drugs when human efficacy studies are not ethical. While the therapeutic doses of raxibacumab, a monoclonal antibody for the prophylaxis and treatment of inhalational anthrax, have been based on pharmacokinetic data from adult subjects, its disposition in children has not been investigated in clinical trials. Here we evaluate the effect of demographic covariates and maturation processes on the pharmacokinetics of raxibacumab and explore opportunities for the optimisation of paediatric doses., Methods: A population pharmacokinetic model was used as basis for the extrapolation of raxibacumab disposition from adults to children. Different extrapolation scenarios, including weight-banded dosing regimens, were considered to assess the effect of growth and maturation on the pharmacokinetic parameters of interest. Area under the concentration-time curve, maximum plasma concentration and the time of serum raxibacumab concentrations greater than or equimolar to the highest serum protective antigen concentrations observed for at least 28 days in any monkey challenged with Bacillus anthracis that died were derived and compared with the currently approved US doses., Results: Based on practical considerations, a weight-banded dosing regimen consisting of 4 dose levels (75 mg/kg for individuals ≤1.5 kg, 55 mg/kg for individuals <10 kg, 45 mg/kg for individuals <50 kg, 40 mg/kg for all individuals >50 kg) was required to optimise target exposure across the paediatric population., Conclusions: Age-related maturation processes may affect raxibacumab clearance in very young patients. The proposed dosing regimens take into account effects of body weight and maturation processes on the elimination of raxibacumab., (© 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Px563L is a next-generation anthrax vaccine candidate consisting of a protein subunit, mutant recombinant protective antigen SNKE167-ΔFF-315-E308D (mrPA), and liposome-embedded monophosphoryl lipid A (MPLA) adjuvant. Px563L has the potential to deliver an improved safety and immunogenicity profile relative to the currently licensed vaccine, which is produced from filtered B. anthracis culture supernatants. We conducted a Phase 1, double-blind, placebo-controlled, dose-escalation study in 54 healthy subjects to evaluate Px563L at 3 dose levels of mrPA (10, 50, and 80 mcg). For each dose level, 18 subjects were randomized in an 8:8:2 ratio to Px563L (mrPA with adjuvant), RPA563 (mrPA only) or placebo (saline). Each subject received an intramuscular (IM) injection on Day 0 and Day 28. Primary safety and immunogenicity analysis was conducted after all subjects completed the Day70 visit, a duration deemed clinically relevant for post-exposure prophylaxis. Long-term safety was assessed through Day 393. Vaccinations with Px563L at all dose levels were well-tolerated. There were no serious adverse events or adverse events (AE) leading to early withdrawal. In all treatment groups, most AEs were due to injection site reactions, and all AEs at the 10 and 50 mcg dose levels were mild. For the primary immunogenicity endpoint (protective toxin neutralizing antibody 50% neutralization factor [TNA NF 50 ]), titers started to increase significantly after the second administration of Px563L, from Day35 through Day70, with the geometric mean and lower bound of the 95% confidence interval exceeding 0.56, a threshold correlating with significant survival in animal models of anthrax exposure. In conclusion, Px563L, administered as two IM doses 28 days apart, was well-tolerated and elicited a protective antibody response starting at seven days after the second vaccination. These findings support the continued development of Px563L in a two-dose regimen for anthrax post-exposure prophylaxis. ClinicalTrials.gov identifier NCT02655549., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Diane Retallack is an employee of Ligand Pharmaceuticals., which has acquired Pfenex Inc, the study sponsor. Carrie Schneider and Hubert Chen are former employees of Pfenex Inc. Edgar Bautista was compensated by contract with Pfenex Inc., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Anthrax is endemic in Ethiopia with sporadic outbreaks despite the regular vaccination of domestic livestock. This has raised concerns on the effectiveness of the vaccination strategy which may be associated with breaches in the vaccine cold chain maintenance. This study was aimed at demonstrating the tolerance of anthrax vaccine to cold chain breaches through evaluation of viable spore counts expressed as colony forming units per mL (CFU/mL) of freeze-dried and suspension anthrax vaccines stored at 5 °C, 20 °C and 37 °C for up to 6 months. Both vaccine formulations maintained above the recommended minimum required titre (2 × 10 6 culturable spores per dose for cattle, buffaloes and horses, and not <1 × 10 6 for sheep and goats) for up to 6 months at 5 °C storage. In storage at 20 °C, the viability of freeze-dried anthrax vaccine maintained the minimum required titre up to 6 months while up to 90 days in case of the suspension formulation. Both types of vaccine formulations maintained the minimum titre per dose for up to 30 days at 37 °C storage. Generally, both vaccine formulations showed similar trends in titre fall in all of the three storage temperatures (5 °C, 20 °C and 37 °C) as observed in the almost linearly overlapping 95% confidence intervals (CI) up to day 90 at 5 °C and 20 °C storages while up to day 30 at 37 °C storage. However, a significant (P < 0.05) drop in titre was observed after day 90 for storages at 5 °C and 20 °C, and after day 30 for 37 °C storage as observed in the non overlapping 95% CI from the average titres of previous time points. This study showed that if temperature excursion occurs above the recommended temperature range (4-8 °C) during storage or transport, the vaccine should remain effective and can still be used in vaccination programs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Bacillus anthracis is a zoonotic bacterium that affects wide numbers of vertebrate animals and man and has life threating potential both in animal s as well as humans., Methods: A cross sectional study was conducted to assess the knowledge about, attitudes towards, and practices addressing (KAPs) anthrax among community members in selected upazillas' of Meherpur and Sirajgonj districts for the prevention and control of anthrax using a structured questionnaire., Results: A total of 424 community members were considered in this study irrespective of their age and sex. Most of the respondents were female (57.54%) and about half were illiterate (47.40%). Most of the respondents (86.32%) were self-employed with crop and livestock farming. Among the self-employed farmers, cattle (63.73%) were the highest reared animals. Among the respondents, 37.26% had no knowledge about anthrax. On the other hand, among the existing knowledge level, 46.69% received information of anthrax from neighbour, 74.05% and 56.82% were concerned about the mode of transmission of anthrax from animal to human through eating, handling and soil. Respondents usually collected vaccine from quack (58.25%) and vaccination status was highest in Kamarkhand (52.03%) and lowest in Gangni upazilla (10.82%). Overall 62.74% community members considered that anthrax is a fatal disease for livestock and 82.54% people disposed carcass in buried method., Conclusion: The study findings indicated that the community members had average knowledge on cause, symptoms, transmission and prevention of anthrax. The supplied vaccine was found negligible with the number of livestock in the studied upazilas. Veterinary and Medical health planners should design and implement interventions for awareness building on anthrax under One Health (OH) approach for educating the community people on anthrax control and prevention., (© 2021 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Background: Anthrax is a zoonotic disease that can be transmitted to humans from infected animals. During May-June 2017, three persons with probable cutaneous anthrax were reported in Arua District, Uganda; one died. All had recently handled carcasses of livestock that died suddenly and a skin lesion from a deceased person tested positive by PCR for Bacillus anthracis. During July, a bull in the same community died suddenly and the blood sample tested positive by PCR for Bacillus anthracis. The aim of this investigation was to establish the scope of the problem, identify exposures associated with illness, and recommend evidence-based control measures., Methods: A probable case was defined as acute onset of a papulo-vesicular skin lesion subsequently forming an eschar in a resident of Arua District during January 2015-August 2017. A confirmed case was a probable case with a skin sample testing positive by polymerase chain reaction (PCR) for B. anthracis. Cases were identified by medical record review and active community search. In a case-control study, exposures between case-patients and frequency- and village-matched asymptomatic controls were compared. Key animal health staff were interviewed to learn about livestock deaths., Results: There were 68 case-patients (67 probable, 1 confirmed), and 2 deaths identified. Cases occurred throughout the three-year period, peaking during dry seasons. All cases occurred following sudden livestock deaths in the villages. Case-patients came from two neighboring sub-counties: Rigbo (attack rate (AR) = 21.9/10,000 population) and Rhino Camp (AR = 1.9/10,000). Males (AR = 24.9/10,000) were more affected than females (AR = 0.7/10,000). Persons aged 30-39 years (AR = 40.1/10,000 population) were most affected. Among all cases and 136 controls, skinning (ORM-H = 5.0, 95%CI: 2.3-11), butchering (ORM-H = 22, 95%CI: 5.5-89), and carrying the carcass of livestock that died suddenly (ORM-H = 6.9, 95%CI: 3.0-16) were associated with illness., Conclusions: Exposure to carcasses of animals that died suddenly was a likely risk factor for cutaneous anthrax in Arua District during 2015-2017. The recommendations are investigation of anthrax burden in livestock, prevention of animal infections through vaccinations, safe disposal of the carcasses, public education on risk factors for infection and prompt treatment of illness following exposure to animals that died suddenly., Competing Interests: The authors have declared that no competing interests exist.