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Anthrax is a zoonotic infectious disease caused by Bacillus anthracis. According to current knowledge, the disease originates in sub-Saharan Africa, especially Egypt and Mesopotamia. Laboratory tests involving direct staining or culture of samples taken from malignant pustules, sputum, blood, or patient discharge must be performed to establish a diagnosis. B. anthracis infection can enter the body through the skin, mouth, or nose. Human infection is usually caused by contact with infected animals or animal products. Anthrax causes a reduction in resource efficiency and decreases livestock productivity. B. anthracis spores are resistant to extreme temperatures, pressure, pH, drying, solvents, and ultraviolet light. The biological weapon of this disease may be fatal if it is designed to spread B. anthracis spores by aerosols. In the past, the treatment of human anthrax with penicillin at a high dose was the preferred method. The public can take several measures to prevent anthrax infection, such as purchasing and consuming meat that has been legally certified to have been slaughtered in a slaughterhouse, consuming healthy and properly cooked animal meat, and washing hands with antiseptic soap after handling, processing, and cooking animal products. This review aimed to describe the etiology, pathogenesis, mechanism of infection, epidemiology, diagnosis, clinical symptoms, transmission, risk factors, public health importance, economic impact, potential as a bio-warfare agent, treatment, and control of anthrax.

Bacillus anthracis causes anthrax through virulence factors encoded on two plasmids. However, non-B. anthracis organisms within the closely related, environmentally ubiquitous Bacillus cereus group (BCG) may cause an anthrax-like disease in humans through the partial adoption of anthrax-associated virulence genes, challenging the definition of anthrax disease. To elucidate these phenomena and their evolutionary past, we performed whole-genome sequencing on non-anthracis BCG isolates, including 93 archival (1967–2003) and 5 contemporary isolates (2019–2023). We produced annotated genomic assemblies and performed a pan-genome analysis to identify evidence of virulence gene homology and virulence gene acquisition by linear inheritance or horizontal gene transfer. At least one anthrax-associated virulence gene was annotated in ten isolates. Most homologous sequences in archival isolates showed evidence of pseudogenization and subsequent gene loss. The presence or absence of accessory genes, including anthrax-associated virulence genes, aligned with the phylogenetic structure of the BCG core genome. These findings support the hypothesis that anthrax-associated virulence genes were inherited from a common ancestor in the BCG and were retained or lost across different lineages, and contribute to a growing body of work informing public health strategies related to anthrax surveillance and identification.

Anthrax is a notorious disease of public health importance caused by Bacillus anthracis. The causative agent can also be used as a biological weapon. Spores of these bacteria can sustain extreme environmental conditions and remain viable in soil for decades. Domestic and wild ruminants are highly susceptible to this pathogen, which usually presents as a peracute to acute disease. In humans, cutaneous anthrax is frequent but pulmonary and enteric anthrax are more serious. Humans, animals, and the environment are all involved, making anthrax a perfect target for a One Health approach. The environment plays a key role in disease transmission. At a time when the One Health concept is not mere slogans, collaborative efforts of medical professionals, veterinarians, and environmental scientists will be valuable for the prevention and control of this disease. In this review, we discussed the transmission dynamics of anthrax in the environment, animals, and humans, as well as One Health strategies to control and prevent anthrax.

Anthrax, a zoonotic disease affecting both livestock and humans globally, is caused by Bacillus anthracis. The objectives of this study were the following: (1) to identify environmental risk factors for anthrax and use this information to develop an improved predictive risk map, and (2) to estimate spatial variation in basic reproduction number (Ro) and herd immunity threshold at the village level, which can be used to optimize vaccination policies within high-risk regions. Based on the anthrax incidences from 2000–2023 and vaccine administration figures between 2008 and 2022 in Karnataka, this study depicted spatiotemporal pattern analysis to derive a risk map employing machine learning algorithms and estimate Ro and herd immunity threshold for better vaccination coverage. Risk factors considered were key meteorological, remote sensing, soil, and geographical parameters. Spatial autocorrelation and SaTScan analysis revealed the presence of hotspots and clusters predominantly in the southern, central, and uppermost northern districts of Karnataka and temporal cluster distribution between June and September. Factors significantly associated with anthrax were air temperature, surface pressure, land surface temperature (LST), enhanced vegetation index (EVI), potential evapotranspiration (PET), soil temperature, soil moisture, pH, available potassium, sulphur, and boron, elevation, and proximity to waterbodies and waterways. Ensemble technique with random forest and classification tree models were used to improve the prediction accuracy of anthrax. High-risk areas are expected in villages in the southern, central, and extreme northern districts of Karnataka. The estimated Ro revealed 11 high-risk districts with Ro > 1.50 and respective herd immunity thresholds ranging from 11.24% to 55.47%, and the assessment of vaccination coverage at the 70%, 80%, and 90% vaccine efficacy levels, all serving for need-based strategic vaccine allocation. A comparison analysis of vaccinations administered and vaccination coverage estimated in this study is used to illustrate difference in the supply and vaccine force. The findings from the present study may support in planning preventive interventions, resource allocation, especially of vaccines, and other control strategies against anthrax across Karnataka, specifically focusing on predicted high-risk regions.

Bacillus anthracis is a rare but highly dangerous zoonotic bacterial pathogen. At the beginning of this century, a new manifestation of the disease, injectional anthrax, emerged as a result of recreational heroin consumption involving contaminated drugs. The organisms associated with this 13-year-lasting outbreak event in European drug consumers were all grouped into the canonical single-nucleotide polymorphism (canSNP) clade A-branch (A.Br.) 161 of B. anthracis. Related clade A.Br.161 strains of B. anthracis not associated with heroin consumption have also been identified from different countries, mostly in Asia. Because of inadvertent spread by anthropogenic activities, other strains of this A.Br.161 lineage were, however, isolated from several countries. Thus, without additional isolates from this clade, its origin of evolution or its autochthonous region remains obscure. Here, we genomically characterized six new A.Br.161 group isolates, some of which were from Iran, with others likely historically introduced into Germany. All the chromosomes of these isolates could be grouped into a distinct sub-clade within the A.Br.161 clade. This sub-clade is separated from the main A.Br.161 lineage by a single SNP. We have developed this SNP into a PCR assay facilitating the future attribution of strains to this group.

Abstract Anthrax outbreaks in Ghana have become a pressing public health concern, posing threats to human health, the agricultural sector, and social well‐being. This letter to the editor highlights the gravity of the anthrax situation in Ghana and advocates for comprehensive interventions using a One Health approach. The epidemiology of anthrax, including its historical roots and modes of transmission, is discussed. The consequences of anthrax outbreaks, such as severe illness, economic losses, and social distress, are outlined. To combat this complex issue, the letter emphasizes the importance of enhanced awareness, prevention, accurate diagnosis, and timely treatment. Recommendations include vaccination of animals and humans, education campaigns, proper disposal of infected carcasses, strengthening healthcare systems, surveillance, and early detection. Collaboration and coordination among professionals in the human, animal, and environmental sectors are crucial. By adopting a One Health approach and implementing these measures, Ghana can effectively mitigate the impact of anthrax outbreaks and safeguard the health and well‐being of its population and livestock.

ObjectiveTo determine the epidemic characteristics of anthrax in Chengde City， Hebei Province from 2005 to 2021， and to provide evidence for formulating prevention and control measures of anthrax and reducing incidence rate.MethodsThis study collected the data of anthrax epidemic in Chengde City and conducted descriptive analysis.ResultsFrom 2005 to 2021， a total of 11 anthrax cases were reported in Chengde City with no death. The average incidence rate was 0.08/105， which remained low. Furthermore， 10 cases were cutaneous anthrax and 1 case was pulmonary anthrax. The cases were mainly reported in Weichang County， accounting for 90.91% of the total reported cases， followed by Pingquan City. In addition， the cases were mainly reported from July to August and mainly between 30 and 59 years old with a gender ratio of 2.67∶1.ConclusionThe anthrax epidemic in Chengde City is likely to increase. It mainly occurs in summer， rural areas， and male young and middle-aged farmers. It is necessary to improve epidemic monitoring， health education， disease prevention capacity， early identification of the epidemic， and active response.

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.

Whole-genome sequencing (WGS) is being applied increasingly to Bacillus cereus group species; however, misinterpretation of WGS results may have severe consequences. We report 3 cases, 1 of which was an outbreak, in which misinterpretation of B. cereus group WGS results hindered communication within public health and industrial laboratories.

Vaccination against Bacillus anthracis is the best preventive measure against the development of deadly anthrax disease in the event of exposure to anthrax either as a bioweapon or in its naturally occurring form. Anthrax vaccines, however, have historically been plagued with controversy, particularly related to their safety. Fortunately, recent improvements in anthrax vaccines have been shown to confer protection with reduced short-term safety concerns, although questions about long-term safety remain. Here, we (a) review recent and ongoing advances in anthrax vaccine development, (b) emphasize the need for thorough characterization of current (and future) vaccines, (c) bring to focus the importance of host immunogenetics as the ultimate determinant of successful antibody production and protection, and (d) discuss the need for the systematic, active, and targeted monitoring of vaccine recipients for possible Chronic Multisymptom Illness (CMI).

Institut Pasteur and Bacillus anthracis have enjoyed a relationship lasting almost 120 years, starting from its foundation and the pioneering work of Louis Pasteur in the nascent fields of microbiology and vaccination, and blooming after 1986 following the molecular biology/genetic revolution. This contribution will give a historical overview of these two research eras, taking advantage of the archives conserved at Institut Pasteur. The first era mainly focused on the production, characterisation, surveillance and improvement of veterinary anthrax vaccines; the concepts and technologies with which to reach a deep understanding of this research field were not yet available. The second period saw a new era of B. anthracis research at Institut Pasteur, with the anthrax laboratory developing a multi-disciplinary approach, ranging from structural analysis, biochemistry, genetic expression, and regulation to bacterial-host cell interactions, in vivo pathogenicity, and therapy development; this led to the comprehensive unravelling of many facets of this toxi-infection. B. anthracis may exemplify some general points on how science is performed in a given society at a given time and how a scientific research domain evolves. A striking illustration can be seen in the additive layers of regulations that were implemented from the beginning of the 21st century and their impact on B. anthracis research. B. anthracis and anthrax are complex systems that raise many valuable questions regarding basic research. One may hope that B. anthracis research will be re-initiated under favourable circumstances later at Institut Pasteur.

Due to several factors, such as environmental and climate changes, the risk of health threats originating at the human–animal–environment interface, including vector-borne diseases (VBDs) and zoonoses, is increasing. Low-resource settings struggle to counter these multidimensional risks due to their already-strained health systems and are therefore disproportionally affected by the impact caused by these changes. Systemic approaches like One Health (OH) are sought to strengthen prevention and preparedness strategies by addressing the drivers of potential threats with a multidisciplinary and multisectoral approach, considering the whole system at the human–animal–environment interface. The integration of OH in national plans can be challenging due to the lack of effective coordination and collaboration among different sectors. To support the process of knowledge coproduction about the level of OH integration in prevention and preparedness strategies against health threats in Armenia, a situation analysis was performed on Crimean–Congo hemorrhagic fever/virus and anthrax (identified by local stakeholders as priorities to be addressed with the OH approach), and actions to strengthen the national OH system were identified with the support of a OH conceptual framework. The study highlighted that multidisciplinary and multisectoral efforts towards prevention and preparedness against VBDs and zoonoses threats need to be strengthened in Armenia, and priority actions to integrate the OH approach were identified.

Anthrax is a particularly dangerous infection of humans and ungulates caused by the Gram-positive spore-forming bacterium Bacillus anthracis. The highly monomorphic and clonal species B. anthracis is commonly divided into three main lineages, A, B, and C, which in turn are divided into several canSNP groups. We report here a phylogenetic analysis based on the whole-genome sequence (WGS) data of fifteen strains isolated predominantly in Siberia or Central and Southern Russia. We confirm the wide distribution of the cluster of strains of the B.Br.001/002 group, endemic to the Russian Arctic, which is also present in the steppe zone of Southern Siberia. We characterize additional branches within the major A.Br.001/002 polytomy comprising the A.Br.Ames and A.Br.Sterne lineages, one of which is identified in the Arctic.

Anthrax is a disease of concern in many mammals, including humans. Management primarily consists of prevention through vaccination and tracking clinical-level observations because environmental isolation is laborious and bacterial distribution across large geographic areas difficult to confirm. Feral swine (Sus scrofa) are an invasive species with an extensive range in the southern United States that rarely succumbs to anthrax. We present evidence that feral swine might serve as biosentinels based on comparative seroprevalence in swine from historically defined anthrax-endemic and non–anthrax-endemic regions of Texas. Overall seropositivity was 43.7% (n = 478), and logistic regression revealed county endemicity status, age-class, sex, latitude, and longitude were informative for predicting antibody status. However, of these covariates, only latitude was statistically significant (β = –0.153, p = 0.047). These results suggests anthrax exposure in swine, when paired with continuous location data, could serve as a proxy for bacterial presence in specific areas.

Anthrax toxin is a critical virulence factor of Bacillus anthracis. The toxin comprises protective antigen (PA) and two enzymatic moieties, edema factor (EF) and lethal factor (LF), forming bipartite lethal toxin (LT) and edema toxin (ET). PA binds cellular surface receptors and is required for intracellular translocation of the enzymatic moieties. For this reason, anti-PA antibodies have been developed as therapeutics for prophylaxis and treatment of human anthrax infection. Assays described publicly for the control of anti-PA antibody potency quantify inhibition of LT-mediated cell death or the ET-induced increase in c-AMP levels. These assays do not fully reflect and/or capture the pathological functions of anthrax toxin in humans. Herein, we report the development of a cell-based gene reporter potency assay for anti-PA antibodies based on the rapid LT-induced degradation of c-Jun protein, a pathogenic effect that occurs in human cells. This new assay was developed by transducing Hepa1c1c7 cells with an AP-1 reporter lentiviral construct and has been qualified for specificity, accuracy, repeatability, intermediate precision, and linearity. This assay not only serves as a bioassay for LT activity, but has applications for characterization and quality control of anti-PA therapeutic antibodies or other products that target the AP-1 signaling pathway.

(1) Background: Bacillus cereus biovar anthracis (Bcbva) was the causative agent of an anthrax-like fatal disease among wild chimpanzees in 2001 in Côte d’Ivoire. Before this, there had not been any description of an anthrax-like disease caused by typically avirulent Bacillus cereus. Genetic analysis found that B. cereus had acquired two anthrax-like plasmids, one a pXO1-like toxin producing plasmid and the other a pXO2-like plasmid encoding capsule. Bcbva caused animal fatalities in Cameroon, Democratic Republic of Congo, and the Central African Republic between 2004 and 2012. (2) Methods: The pathogen had acquired plasmids in the wild and that was discovered as the cause of widespread animal fatalities in the early 2000s. Primate bones had been shipped out of the endemic zone for anthropological studies prior to the realized danger of contamination with Bcbva. Spores were isolated from the bone fragments and positively identified as Bcbva. Strains were characterized by classical microbiological methods and qPCR. Four new Bcbva isolates were whole-genome sequenced. Chromosomal and plasmid phylogenomic analysis was performed to provide temporal and spatial context to these new strains and previously sequenced Bcbva. Tau and principal component analyses were utilized to identify genetic and spatial case patterns in the Taï National Park anthrax zone. (3) Results: Preliminary studies positively identified Bcbva presence in several archival bone fragments. The animals in question died between 1994 and 2010. Previously, the earliest archival strains of Bcbva were identified in 1996. Though the pathogen has a homogeneous genome, spatial analyses of a subset of mappable isolates from Taï National Park revealed strains found closer together were generally more similar, with strains from chimpanzees and duikers having the widest distribution. Ancestral strains were located mostly in the west of the park and had lower spatial clustering compared to more recent isolates, indicating a local increase in genetic diversity of Bcbva in the park over space and time. Global clustering analysis indicates patterns of genetic diversity and distance are shared between the ancestral and more recently isolated type strains. (4) Conclusions: Our strains have the potential to unveil historical genomic information not available elsewhere. This information sheds light on the evolution and emergence of a dangerous anthrax-causing pathogen.

Climatic changes have already resulted and will continue to result in gradual degradation of active upper layers in permafrost due to increased average air temperature in summer. Anthrax is an example of a climate-depending bacterial infection; anthrax agent creates spores that remain viable for a long period of time they spend in cryptobiosis in permafrost. Apparent permafrost degradation is already detected in most arctic regions in Russia and it can lead to anthrax burials decay thus creating elevated risks of the infection among farm animals and people who live on these territories. Our research goal was to create specific zones in municipal districts via combining data on permafrost, number of anthrax cattle burials, ascending trends in average long-term temperatures, and population density. We developed two relative hazard coefficients for characterizing anthrax outbreaks probability for animals and local population. Basing on numeric values obtained for these two coefficients, 70 administrative districts located in 15 RF subjects in the Arctic zone were listed in a descending order as per risks of the infection occurrence. We created two score scales showing relative hazard; they indicated that the highest population risk was typical for urban districts as population density there was much high than in rural ones. Our calculations should be helpful for determining priorities when preventive activities are developed on arctic and sub-arctic territories that are endemic as per anthrax. It is also important to obtain an actual list of cattle burials and to develop spatial-time models showing anthrax outbreaks occurrence taking into account climatic warming and permafrost degradation.

Anthrax is a disease that affects livestock, wildlife, and humans worldwide; however, its relative impacts on these populations remain underappreciated. Feral swine (Sus scrofa) are relatively resistant to developing anthrax, and past serosurveys have alluded to their utility as sentinels, yet empirical data to support this are lacking. Moreover, whether feral swine may assist in the dissemination of infectious spores is unknown. To address these knowledge gaps, we intranasally inoculated 15 feral swine with varying quantities of Bacillus anthracis Sterne 34F2 spores and measured the seroconversion and bacterial shedding over time. The animals also were inoculated either one or three times. The sera were evaluated by enzyme-linked immunosorbent assay (ELISA) for antibodies against B. anthracis, and nasal swabs were cultured to detect bacterial shedding from the nasal passages. We report that the feral swine developed antibody responses to B. anthracis and that the strength of the response correlated with the inoculum dose and the number of exposure events experienced. Isolation of viable bacteria from the nasal passages of the animals throughout the study period suggests that feral swine may assist in the spread of infectious spores on the landscape and have implications for the identification of environments contaminated with B. anthracis as well as the exposure risk to more susceptible hosts.

On April 20, 2018, the Kween District Health Office in Kween District, Uganda reported 7 suspected cases of human anthrax. A team from the Uganda Ministry of Health and partners investigated and identified 49 cases, 3 confirmed and 46 suspected; no deaths were reported. Multiple exposures from handling the carcass of a cow that had died suddenly were significantly associated with cutaneous anthrax, whereas eating meat from that cow was associated with gastrointestinal anthrax. Eating undercooked meat was significantly associated with gastrointestinal anthrax, but boiling the meat for >60 minutes was protective. We recommended providing postexposure antimicrobial prophylaxis for all exposed persons, vaccinating healthy livestock in the area, educating farmers to safely dispose of animal carcasses, and avoiding handling or eating meat from livestock that died of unknown causes.

The zoonotic disease anthrax is endemic to most continents. It is a disease of herbivores that incidentally infects humans through contact with animals that are ill or have died from anthrax or through contact with Bacillus anthracis–contaminated byproducts. In the United States, human risk is primarily associated with handling carcasses of hoofstock that have died of anthrax; the primary risk for herbivores is ingestion of B. anthracis spores, which can persist in suitable alkaline soils in a corridor from Texas through Montana. The last known naturally occurring human case of cutaneous anthrax associated with livestock exposure in the United States was reported from South Dakota in 2002. Texas experienced an increase of animal cases in 2019 and consequently higher than usual human risk. We describe the animal outbreak that occurred in southwest Texas beginning in June 2019 and an associated human case. Primary prevention in humans is achieved through control of animal anthrax.

Human anthrax cases necessitate rapid response. We completed Bacillus anthracis nanopore whole-genome sequencing in our high-containment laboratory from a human anthrax isolate hours after receipt. The de novo assembled genome showed no evidence of known antimicrobial resistance genes or introduced plasmid(s). Same-day genomic characterization enhances public health emergency response.

The causative agent of anthrax, Bacillus anthracis, evades the host immune response and establishes infection through the production of binary exotoxins composed of Protective Antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). The majority of vaccination strategies have focused upon the antibody response to the PA subunit. We have used a panel of humanised HLA class II transgenic mouse strains to define HLA-DR-restricted and HLA-DQ-restricted CD4+ T cell responses to the immunodominant epitopes of PA. This was correlated with the binding affinities of epitopes to HLA class II molecules, as well as the responses of two human cohorts: individuals vaccinated with the Anthrax Vaccine Precipitated (AVP) vaccine (which contains PA and trace amounts of LF), and patients recovering from cutaneous anthrax infections. The infected and vaccinated cohorts expressing different HLA types were found to make CD4+ T cell responses to multiple and diverse epitopes of PA. The effects of HLA polymorphism were explored using transgenic mouse lines, which demonstrated differential susceptibility, indicating that HLA-DR1 and HLA-DQ8 alleles conferred protective immunity relative to HLA-DR15, HLA-DR4 and HLA-DQ6. The HLA transgenics enabled a reductionist approach, allowing us to better define CD4+ T cell epitopes. Appreciating the effects of HLA polymorphism on the variability of responses to natural infection and vaccination is vital in planning protective strategies against anthrax.

During March 13–June 23, 2018, anthrax-like cutaneous lesions attributed to the Bacillus cereus group of organisms developed in 12 newborns in India. We traced the source of infection to the healthcare kits used for newborn care. We used multilocus sequence typing to characterize the 19 selected strains from various sources in hospital settings, including the healthcare kits. This analysis revealed the existence of a genetically diverse population comprising mostly new sequence types. Phylogenetic analysis clustered most strains into the previously defined clade I, composed primarily of pathogenic bacilli. We suggest that the synergistic interaction of nonhemolytic enterotoxin and sphingomyelinase might have a role in the development of cutaneous lesions. The infection was controlled by removing the healthcare kits and by implementing an ideal housekeeping program. All the newborns recovered after treatment with ciprofloxacin and amikacin.

In late September 2017, Bwabwata National Park in Namibia experienced a sudden die-off of hippopotamuses and Cape buffalo. A multiorganizational response was initiated, involving several ministries within Namibia and the US Centers for Disease Control and Prevention. Rapid interventions resulted in zero human or livestock cases associated with this epizootic.

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

Anthrax-causing members of Bacillus cereus sensu lato (s.l.) pose a serious threat to public health. While most anthrax-causing strains resemble B. anthracis phenotypically, rare cases of anthrax-like illness caused by strains resembling “B. cereus” have been reported. Here, whole-genome sequencing was used to characterize three B. cereus s.l. isolates associated with two 2020 welder anthrax cases in the United States, which resembled “B. cereus” phenotypically. Comparison of the three genomes sequenced here to all publicly available, high-quality B. cereus s.l. genomes (n = 2890 total genomes) demonstrated that genomes associated with each case effectively belonged to separate species at the conventional 95% average nucleotide identity prokaryotic species threshold. Two PubMLST sequence type 78 (ST78) genomes affiliated with a case in Louisiana were most closely related to B. tropicus and possessed genes encoding the Bps exopolysaccharide capsule, as well as hemolysin BL (Hbl) and cytotoxin K (CytK). Comparatively, a ST108 genome associated with a case in Texas was most closely related to B. anthracis; however, like other anthrax-causing strains most closely related to B. anthracis, this genome did not possess Bps-, Hbl-, or CytK-encoding genes. Overall, results presented here provide insights into the evolution of anthrax-causing B. cereus s.l.

Purpose: This study aims to analyze and characterize anthrax vaccine-related research, key developments, global research trends, and mapping of published scientific research articles during the last three decades (1991–2021). Methods: A bibliometric and visualized study was conducted. The Web of Science Core Collection database (WoSCC) was searched using relevant keywords (“Anthrax” OR “Anthrax bacterium” OR “Bacillus anthracis” OR “Bacteridium anthracis” OR “Bacillus cereus var. Anthracis” (Topic)) AND (“Vaccine” OR “Vaccines” OR “Immunization” OR “Immunisation” OR “Immunizations” OR “Immunisations” (Topic)) with specific restrictions. The data was analyzed and plotted by using different bibliometric software and tools (HistCiteTM software, version 12.3.17, Bibliometrix: An R-tool version 3.2.1, and VOSviewer software, version 1.6.17). Results: The initial search yielded 1750 documents. After screening the titles and abstracts of the published studies, a total of 1090 articles published from 1991 to 2021 were included in the final analysis. These articles were published in 334 journals and were authored by 4567 authors from 64 countries with a collaboration index of 4.32. The annual scientific production growth rate was found to be 9.68%. The analyzed articles were cited 31335 times. The most productive year was 2006 (n = 77, 7.06%), while the most cited year was 2007 (2561 citations). The leading authors and journals in anthrax research were Rakesh Bhatnagar from Jawaharlal Nehru University, India (n = 35, 3.21%), and Vaccine (n = 1830, 16.51%), while the most cited author and journal were Arthur M. Friedlander from the United States Department of Defense (n = 2762), and Vaccine (n = 5696), respectively. The most studied recent research trend topics were lethal, double-blind, epidemiology, B surface antigen, disease, and toxin. The United States of America (USA) was the most dominant country in terms of publications, citations, corresponding author country, and global collaboration in anthrax vaccine research. The USA had the strongest collaboration with the United Kingdom (UK), China, Canada, Germany, and France. Conclusion: This is the first bibliometric study that provides a comprehensive historical overview of scientific studies. From 2006 to 2008, more than 20% of the total articles were published; however, a decrease was observed since 2013 in anthrax vaccine research. The developed countries made significant contributions to anthrax vaccine-related research, especially the USA. Among the top 10 leading authors, six authors are from the USA. The majority of the top leading institutions are also from the USA. About 90% of the total studies were funded by the United States Department of Health and Human Services (HHS), National Institutes of Health (NIH), USA, and the National Institute of Allergy and Infectious Diseases (NIAID), USA.

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

We present the case of a 57-old-year male patient with a past medical history of hypertension and type 2 diabetes mellitus, who presented to the surgical emergency department of the "Guillermo Domínguez López" General Teaching Hospital of the municipality of Puerto Padre, Las Tunas. The patient stated that five days before he had scratched a lesion in the back and from then on he noticed a volume growth, pain, burning, flush, fever and general malaise. On physical examination a volume growth in the region with a diameter of 20 cm was revealed, with multiple postulant orifices with hardened borders and a fluctuating center. The patient was admitted and emergency investigations were ordered. After 12 hours the patient was operated on with a crucial incision of the lesion, debridement and lining lifting. Gauze compresses with antibiotic cream were left. After ten days of surgery the wall was closed. Follow-up was appointed and at three months the patient was definitely discharged, with a total recovery and without the need to apply grafts.

INTRODUCTION: Anthrax is endemic in some parts of Kenya causing mortalities in livestock and morbidity in humans. On January 20, 2018, news media reported suspected anthrax in a remote southern Kenyan village after villagers became ill following consumption of meat from a dead cow that was confirmed, by microscopy, to have died of anthrax. We assessed community knowledge, attitude and practices (KAP) to identify intervention gaps for anthrax prevention. METHODS: we conducted a KAP survey in randomly selected households (HHs) in villages from selected wards. Using multi-stage sampling approach, we administered structured questionnaire to persons aged ≥15 years to collect KAP information from February 11-21, 2018. From a set of questions for KAP, we scored participants’ response as “1” for a correct response and “0” for an incorrect response. Univariate analysis and Chi-square tests were performed to explore determinants of KAP. Concurrently, we gathered qualitative data using interview guides for thematic areas on anthrax KAP from key informant interviews and focus group discussions. Qualitative data were transcribed in Ms Word and analyzed along themes by content analysis. RESULTS: among 334 respondents: 187/334 (56%) were male; mean age, 40.7±13.6 years; 331/334 (99.1%) had heard of anthrax and 304/331(91.8%) knew anthrax to be zoonotic. Transmission was considered to be through eating dead-carcasses by 273/331 (82.5%) and through contact with infected tissue by 213/331 (64.4%). About 59% (194/329) regularly vaccinated their livestock against anthrax, 53.0% (174/328) had slaughtered or skinned a dead-animal and 59.5% (195/328) practiced home slaughter while 52.9% (172/325) treated sick-animals by themselves. Sex (p=0.001), age (p=0.007) and livestock-rearing years (p=0.001) were significantly associated with knowledge and practice. CONCLUSION: there were differences in knowledge and practices towards anthrax by age-group and sex. Enhanced public health education and targeted interventions by relevant government agencies is recommended.

Anthrax is an acute disease caused by the bacterium Bacillus anthracis, and is a potential biowarfare/bioterrorist agent. Its pulmonary form, caused by inhalation of the spores, is highly lethal and is mainly related to injury caused by the toxins secretion. Antibodies neutralizing the toxins of B. anthracis are regarded as promising therapeutic drugs, and two are already approved by the Federal Drug Administration. We developed a recombinant human-like humanized antibody, 35PA83 6.20, that binds the protective antigen and that neutralized anthrax toxins in-vivo in White New Zealand rabbits infected with the lethal 9602 strain by intranasal route. Considering these promising results, the preclinical and clinical phase one development was funded and a program was started. Unfortunately, after 5 years, the preclinical development was cancelled due to industrial and scientific issues. This shutdown underlined the difficulty particularly, but not only, for an academic laboratory to proceed to clinical development, despite the drug candidate being promising. Here, we review our strategy and some preliminary results, and we discuss the issues that led to the no-go decision of the pre-clinical development of 35PA83 6.20 mAb. Our review provides general information to the laboratories planning a (pre-)clinical development.

Anthrax vaccine adsorbed (AVA) containing protective antigen (PA) is the only FDA-approved anthrax vaccine in the United States. Characterization of the binding of AVA-induced anti-PA human antibodies against the PA antigen after vaccination is crucial to understanding mechanisms of the AVA-elicited humoral immune response. Hydrogen deuterium exchange mass spectrometry (HDX-MS) is often coupled with a short liquid chromatography gradient (e.g., 5–10 min) for the characterization of protein interactions. We recently developed a long-gradient (e.g., 90 min), sub-zero temperature, ultra-high performance liquid chromatography HDX-MS (UPLC-HDX-MS) platform that has significantly increased separation power and limited back-exchange for the analysis of protein samples with high complexity. In this study, we demonstrated the utility of this platform for mapping antibody–antigen epitopes by examining four fully human monoclonal antibodies to anthrax PA. Antibody p1C03, with limited neutralizing activity in vivo, bound to a region on domain 1A of PA. p6C04 and p1A06, with no neutralizing activities, bound to the same helix on domain 3 to prevent oligomerization of PA. We found p6C01 strongly bound to domain 3 on a different helix region. We also identified a secondary epitope for p6C01, which likely leads to the blocking of furin cleavage of PA after p6C01 binding. This novel binding of p6C01 results in highly neutralizing activity. This is the first report of this distinct binding mechanism for a highly neutralizing fully human antibody to anthrax protective antigen. Studying such epitopes can facilitate the development of novel therapeutics against anthrax.

The article, written on the basis of data from the Russian and European archives, is the most complete biography of the famous figure of the Russian medical and veterinary science of the middle of the XIX century Friedrich Brauell, one of the pioneers of anthrax research. The article describes in detail the period of formation of F. Brauell as a scientist – his education received in Germany, visit to the Russian Empire for service, confirmation of academic degree received at homeland. His first steps in the field of teaching and science at Kazan University are discussed in details, his efforts to create a collection of anatomical preparations are described. The main part of the article is devoted to his work in Derpat (Tartu) Veterinary School, where he fully revealed his talent as a major organizer of scientific and educational activities. Particular attention is paid to its study of the problem of anthrax and plague. In addition, the article deals with the issues of his personal life and family for the first time. Thus, the material contained in the article can be useful for scientists studying the history of medicine, infectious diseases and veterinary medicine.

The present article summarizes the materials from literary sources dedicated to the issues of laboratory diagnosis of anthrax. It shows the priority of the development of new methods for the elaboration of highly sensitive test systems and preparations designed for the detection and identification of anthrax bacteria. It outlines the role of express-diagnostics of infectious diseases, which is very important when investigating bioterrorism cases, outbreaks and sporadic cases in humans and animals. Providing with the analysis of different methods for detection of anthrax, the article at the same time focuses on modern molecular diagnostic technologies. It is shown that the basic parameters of diagnostic test systems are sensitivity, specificity and reproducibility of the results. The article presents data on the development of culture media for isolation and identification of anthrax, as well as the possibility of using anthrax bacteriophage for phage-based indication and identification of bacteria.

The present article describes the scientific and methodological development of biotechnological manufacture of test-system components (diagnostic preparations) for instant diagnosis of plague, brucellosis, tularemia, anthrax, cholera. In this regard, in the first place the effective methods for obtaining complete antigenic complexes used for immunizing animals for the purpose of developing highly potent immune sera have been established. These antisera were used in determining optimum parameters of manufacture on the basis of their diagnosticums. Methodical basis of developing magnetic immunosorbents for selective concentration of infectious agents and their instant diagnosis methods has been mentioned. Moreover, the article describes the development of piezoelectric quartz crystal biosensors to detect plague, brucellosis and tularemia pathogens by gravimetric flow injection analysis, allowing to quickly implement the process of reliable identification of a test pathogen in antigen-antibody complex.

We are studying the structures of bacterial toxins that form ion channels and enable macromolecule transport across membranes. For example, the crystal structure of the Staphylococcus aureus α-hemolysin (α-HL) channel in its functional state was confirmed using neutron reflectometry (NR) with the protein reconstituted in membranes tethered to a solid support. This method, which provides sub-nanometer structural information, could also test putative structures of the Bacillus anthracis protective antigen 63 (PA63) channel, locate where B. anthracis lethal factor and edema factor toxins (LF and EF, respectively) bind to it, and determine how certain small molecules can inhibit the interaction of LF and EF with the channel. We report here the solution structures of channel-forming PA63 and its precursor PA83 (which does not form channels) obtained with small angle neutron scattering. At near neutral pH, PA83 is a monomer and PA63 a heptamer. The latter is compared to two cryo-electron microscopy structures. We also show that although the α-HL and PA63 channels have similar structural features, unlike α-HL, PA63 channel formation in lipid bilayer membranes ceases within minutes of protein addition, which currently precludes the use of NR for elucidating the interactions between PA63, LF, EF, and potential therapeutic agents.

Abstract Background Bacillus anthracis, which causes anthrax in humans and animals, is enzootic in parts of the U.S. state of Texas where cases are typically reported in animals annually. The gamma phage lysis assay is a common diagnostic method for identification of B. anthracis and is based on the bacterium’s susceptibility to lysis. This test has been shown to be 97% specific for B. anthracis, as a small number of strains of other Bacillus spp. are known to be susceptible. In this study, we evaluated the performance of a combination of B. anthracis diagnostic assays on 700 aerobic, spore-forming isolates recovered from soil collected in Texas. These assays include phenotypic descriptions, gamma phage susceptibility, and real-time polymerase chain reaction specific for B. anthracis. Gamma phage-susceptible isolates were also tested using cell wall and capsule direct fluorescent-antibody assays specific for B. anthracis. Gamma phage-susceptible isolates that were ruled out as B. anthracis were identified by 16S rRNA gene sequencing. Findings We identified 29 gamma phage-susceptible isolates. One was confirmed as B. anthracis, while the other 28 isolates were ruled out for B. anthracis by the other diagnostic tests. Using 16S rRNA gene sequencing results, we identified these isolates as members of the B. cereus group, Bacillus sp. (not within B. cereus group), Lysinibacillus spp., and Solibacillus silvestris. Based on these results, we report a specificity of 96% for gamma phage lysis as a diagnostic test for B. anthracis, and identified susceptible isolates outside the Bacillus genus. Conclusions In this study we found gamma phage susceptibility to be consistent with previously reported results. However, we identified non-B. anthracis environmental isolates (including isolates from genera other than Bacillus) that are susceptible to gamma phage lysis. To date, susceptibility to gamma phage lysis has not been reported in genera other than Bacillus. Though these isolates are not of clinical origin, description of unexpected positives is important, especially as new diagnostic assays for B. anthracis are being developed based on gamma phage lysis or gamma phage proteins.

In September 2011, a total of 511 human cases of anthrax (Bacillus anthracis) infection and 5 deaths were reported in a game management area in the district of Chama, Zambia, near where 85 hippopotamuses (Hippopotamus amphibious) had recently died of suspected anthrax. The human infections generally responded to antibiotics. To clarify transmission, we conducted a cross-sectional, interviewer-administered household survey in villages where human anthrax cases and hippopotamus deaths were reported. Among 284 respondents, 84% ate hippopotamus meat before the outbreak. Eating, carrying, and preparing meat were associated with anthrax infection. Despite the risk, 23% of respondents reported they would eat meat from hippopotamuses found dead again because of food shortage (73%), lack of meat (12%), hunger (7%), and protein shortage (5%). Chronic food insecurity can lead to consumption of unsafe foods, leaving communities susceptible to zoonotic infection. Interagency cooperation is necessary to prevent outbreaks by addressing the root cause of exposure, such as food insecurity.

Using national surveillance data for 120,111 human anthrax cases recorded during 1955−2014, we analyzed the temporal, seasonal, geographic, and demographic distribution of this disease in China. After 1978, incidence decreased until 2013, when it reached a low of 0.014 cases/100,000 population. The case-fatality rate, cumulatively 3.6% during the study period, has also decreased since 1990. Cases occurred throughout the year, peaking in August. Geographic distribution decreased overall from west to east, but the cumulative number of affected counties increased during 2005−2014. The disease has shifted from industrial to agricultural workers; 86.7% of cases occurred in farmers and herdsmen. Most (97.7%) reported cases were the cutaneous form. Although progress has been made in reducing incidence, this study highlights areas that need improvement. Adequate laboratory diagnosis is lacking; only 7.6% of cases received laboratory confirmation. Geographic expansion of the disease indicates that livestock control programs will be essential in eradicating anthrax.

Health officials lack field-implementable tools for forecasting the effects that a large-scale release of Bacillus anthracis spores would have on public health and hospitals. We created a modeling tool (combining inhalational anthrax caseload projections based on initial case reports, effects of variable postexposure prophylaxis campaigns, and healthcare facility surge capacity requirements) to project hospitalizations and casualties from a newly detected inhalation anthrax event, and we examined the consequences of intervention choices. With only 3 days of case counts, the model can predict final attack sizes for simulated Sverdlovsk-like events (1979 USSR) with sufficient accuracy for decision making and confirms the value of early postexposure prophylaxis initiation. According to a baseline scenario, hospital treatment volume peaks 15 days after exposure, deaths peak earlier (day 5), and recovery peaks later (day 23). This tool gives public health, hospital, and emergency planners scenario-specific information for developing quantitative response plans for this threat.

We studied anthrax immune globulin intravenous (AIG-IV) use from a 2009–2010 outbreak of Bacillus anthracis soft tissue infection in injection drug users in Scotland, UK, and we compared findings from 15 AIG-IV recipients with findings from 28 nonrecipients. Death rates did not differ significantly between recipients and nonrecipients (33% vs. 21%). However, whereas only 8 (27%) of 30 patients at low risk for death (admission sequential organ failure assessment score of 0–5) received AIG-IV, 7 (54%) of the 13 patients at high risk for death (sequential organ failure assessment score of 6–11) received treatment. AIG-IV recipients had surgery more often and, among survivors, had longer hospital stays than did nonrecipients. AIG-IV recipients were sicker than nonrecipients. This difference and the small number of higher risk patients confound assessment of AIG-IV effectiveness in this outbreak.

Anthrax is a zoonotic disease and is caused by Bacillus anthracis which is a Gram-positive, nonmotile, spore-forming rod, found in soil. The spores can remain viable for decades. Transmission occurs naturally in humans by direct contact with infected animals or the contaminated animal products. Anthrax is a major health problem in eastern and southern India, with a significant human incidence because the disease is poorly controlled. Here, we discuss such a case of naturally occurring fatal anthrax in North-East India. A 48-year-old man from Assam presented with seizures, hematemesis, and fever. Apart from altered mental status and nonreactive pupils, his cutaneous and systemic examination was unremarkable. Noncontrast computed tomography head showed multiple hemorrhages. Blood and cerebrospinal fluid showed heavy growth of anthrax Bacilli. He was started on specific antibiotics after the reports, but unfortunately, the patient succumbed to infection. Due to high prevalence of anthrax in the endemic regions, a high degree of suspicion is required to clinch the diagnosis. Early initiation of therapy before developing the intracranial hemorrhagic complications might result in a better outcome. Careful history for a possible exposure to animal carcass or a suspected animal death due to anthrax will also help in early diagnosis of the disease and effective therapy.

Zoonotic diseases accounts for about 75% of emerging infectious disease and can be devastating to both human and animal health globally. A subset of zoonotic diseases is referred to as "neglected zoonotic diseases - NZDs" as they mainly affect poor populations who live in close proximity to domestic or wild animals often in areas where access to health and adequate sanitary facilities are not available. Furthermore, underestimation of the burden of NZD has continually led to its further neglect in least developed countries such as Nigeria. Controlling zoonotic infections including NZDs in animals is crucial in reducing human infections. Veterinarians provides an understanding of the epidemiology of infectious diseases in animal population and are therefore integral for the overall reduction in global burden of NZDs worldwide. Due to the current lack of and in some cases weak involvement of Veterinarians in policy issues related to zoonotic diseases, there is need to elucidate their importance in NZDs control in Nigeria. This review therefore summarises the neglected zoonotic diseases so far documented in Nigeria and also highlight the important role of the Veterinarian in their prevention and control within both human and animal population. Important recommendations to strengthen the role of the public health Veterinarian for sustainable control of NZDs were made.

Anti-toxin agents for severe B. anthracis infection will only be effective if they add to the benefit of the two mainstays of septic shock management, antibiotic therapy and titrated hemodynamic support. Both of these standard therapies could negate benefits related to anti-toxin treatment. At present, three anthrax anti-toxin antibody preparations have received US Food and Drug Administration (FDA) approval: Raxibacumab, Anthrax Immune Globulin Intravenous (AIGIV) and ETI-204. Each agent is directed at the protective antigen component of lethal and edema toxin. All three agents were compared to placebo in antibiotic-treated animal models of live B. anthracis infection, and Raxibacumab and AIGIV were compared to placebo when combined with standard hemodynamic support in a 96 h canine model of anthrax toxin-associated shock. However, only AIG has actually been administered to a group of infected patients, and this experience was not controlled and offers little insight into the efficacy of the agents. To provide a broader view of the potential effectiveness of these agents, this review examines the controlled preclinical experience either in antibiotic-treated B. anthracis models or in titrated hemodynamic-supported toxin-challenged canines. The strength and weaknesses of these preclinical experiences are discussed.

Anthrax is a worldwide zoonotic disease caused by the spore-forming bacterium Bacillus anthracis. Primarily a disease of herbivores, human infections often result from direct contact with contaminated animal products (cutaneous and inhalational anthrax) or through consumption of infected meat (gastrointestinal anthrax). The genetic near neighbor, Bacillus cereus biovar anthracis (Bcbva), causes an anthrax-like illness in the wildlife and livestock of west and central Africa due to the presence and expression of B. anthracis-specific virulence factors in this background. While Bcbva infections have not been reported in humans, a recent seroprevalence study detected Bcbva antibodies in the rural population around Taï National Park. This work describes the development of new TaqMan multiplex PCRs for the simultaneous detection of B. anthracis and Bcbva. The assays are designed to amplify Ba-1, capB, and lef markers in B. anthracis and genomic island IV (GI4), capB, and lef in Bcbva. Our assays allow for the rapid discrimination of B. anthracis and Bcbva and will provide insights into the molecular epidemiology of these two important pathogens that share an overlapping geographical range in west and central Africa.

The US outbreak of B.anthracis infection in 2001 and subsequent cases in the US and Europe demonstrate that anthrax is a continuing risk for the developed world. While several bacterial components contribute to the pathogenesis of B. anthracis, production of lethal toxin (LT) is strongly associated with the development of hypotension and lethality. However, the mechanisms underlying the cardiovascular instability LT produces are unclear. Some evidence suggests that LT causes shock by impairing the peripheral vasculature, effects consistent with the substantial extravasation of fluid in patients dying with B. anthracis. Other data suggests that LT directly depresses myocardial function. However a clinical correlate for this latter possibility is less evident since functional studies and post-mortem examination in patients demonstrate absent or minimal cardiac changes. The purposes of this review were to first present clinical studies of cardiac functional and histologic pathology with B. anthracis infection and to then examine in vivo, in vitro, and ex vivo preclinical studies of LT’s myocardial effects. Together, these data suggest that it is unclear whether that LT directly depresses cardiac function. This question is important for the clinical management and development of new therapies for anthrax and efforts should continue to be made to answer it.

During the First World War, anthrax cases in the United States and England increased greatly and seemed to be associated with use of new shaving brushes. Further investigation revealed that the source material and origin of shaving brushes had changed during the war. Cheap brushes of imported horsehair were being made to look like the preferred badger-hair brushes. Unfortunately, some of these brushes were not effectively disinfected and brought with them a nasty stowaway: Bacillus anthracis. A review of outbreak summaries, surveillance data, and case reports indicated that these cases originated from the use of ineffectively disinfected animal-hair shaving brushes. This historical information is relevant to current public health practice because renewed interest in vintage and animal-hair shaving brushes has been seen in popular culture. This information should help healthcare providers and public health officials answer questions on this topic.

Sterne live spore vaccine (SLSV) is the current veterinary anthrax vaccine of choice. Unlike the non-living anthrax vaccine (NLAV) prototype, SLSV is incompatible with concurrent antibiotics use in an anthrax outbreak scenario. The NLAV candidates used in this study include a crude recombinant protective antigen (CrPA) and a purified recombinant protective antigen (PrPA) complemented by formalin-inactivated spores and Emulsigen-D®/Alhydrogel® adjuvants. Cattle were vaccinated twice (week 0 and 3) with NLAVs plus penicillin-G (Pen-G) treatment and compared to cattle vaccinated twice with SLSV alone and with Pen-G treatment. The immunogenicity was assessed using ELISA against rPA and FIS, toxin neutralisation assay (TNA) and opsonophagocytic assay. The protection was evaluated using an in vivo passive immunisation mouse model. The anti-rPA IgG titres for NLAVs plus Pen-G and SLSV without Pen-G treatment showed a significant increase, whereas the titres for SLSV plus Pen-G were insignificant compared to pre-vaccination values. A similar trend was measured for IgM, IgG1, and IgG2 and TNA titres (NT50) showed similar trends to anti-rPA titres across all vaccine groups. The anti-FIS IgG and IgM titres increased significantly for all vaccination groups at week 3 and 5 when compared to week 0. The spore opsonising capacity increased significantly in the NLAV vaccinated groups including Pen-G treatment and the SLSV without Pen-G but much less in the SLSV group with Pen-G treatment. Passive immunization of A/J mice challenged with a lethal dose of 34F2 spores indicated significant protective capacity of antibodies raised in the SLSV and the PrPA + FIS + adjuvants vaccinated and Pen-G treated groups but not for the NLAV with the CrPA + FIS + adjuvants and the SLSV vaccinated and Pen-G treated group. Our findings indicate that the PrPA + FIS + Emulsigen-D®/Alhydrogel® vaccine candidate may provide the same level of antibody responses and protective capacity as the SLSV. Advantageously, it can be used concurrently with Penicillin-G in an outbreak situation and as prophylactic treatment in feedlots and valuable breeding stocks.

Bacillus anthracis spores that are re-aerosolized from surface deposits after initial contamination present significant health risks for personnel involved in decontamination. To model repeated exposure to low dose B. anthracis spores, three groups of seven rabbits were challenged with multiple low-doses of B. anthracis spores 5 days a week for 3 weeks. Mortality, body temperature, heart and respiration rates, hematology, C-reactive protein, bacteremia, and serum protective antigen were monitored for 21 days post-exposure after the last of multiple doses. All rabbits exposed to a mean daily dose of 2.91 × 102 colony forming units (CFU) survived and showed minimal physiological changes attributable to exposure. One of seven rabbits receiving a mean daily dose of 1.22 × 103 CFU died and four of seven receiving a mean daily dose of 1.17 × 104 CFU died. The LD50 was calculated to be 8.1 × 103 CFU of accumulated dose. Rabbits that succumbed to the higher dose exhibited bacteremia and increases above baseline in heart rate, respiration rate, and body temperature. Two rabbits in the mean daily dose group of 1.17 × 104 CFU exhibited clinical signs of inhalation anthrax yet survived. This study provides a description of lethality, pathophysiology, and pathology in a controlled multiple low-dose inhalation exposure study of B. anthracis in the rabbit model. The data suggest that the accumulated dose is important in survival outcome and that a subset of rabbits may show clinical signs of disease but fully recover without therapeutic intervention