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Bacillus anthracis, the causative agent of anthrax, is among the most likely bacterial pathogens to be used in a biological attack. Inhalation anthrax is a serious, life-threatening form of infection, and the mortality from acute inhaled anthrax can approach 100% if not treated early and aggressively. Food and Drug Administration-approved antibiotics indicated for post-exposure prophylaxis (PEP) or treatment of anthrax are limited. This study assessed the in vitro activity and in vivo efficacy of omadacycline and comparators against clinical isolates of B. anthracis, including a ciprofloxacin-resistant isolate. Minimum inhibitory concentrations (MICs) of omadacycline, ciprofloxacin, and doxycycline were determined against animal and human clinical isolates of B. anthracis, including the ciprofloxacin-resistant Ames strain BACr4-2. Mice were challenged with aerosolized BACr4-2 spores, and survival was monitored for 28 days post-challenge. Treatment was initiated 24 h after aerosol challenge and administered for 14 days. Omadacycline demonstrated in vitro activity against 53 B. anthracis isolates with an MIC range of ≤0.008-0.25 µg/mL, and an MIC50/MIC90 of 0.015/0.03 µg/mL. Consistent with this, omadacycline demonstrated in vivo efficacy in a PEP mouse model of inhalation anthrax caused by the Ames BACr4-2 ciprofloxacin-resistant B. anthracis isolate. Omadacycline treatment significantly increased survival compared with the vehicle control group and the ciprofloxacin treatment group. As antibiotic resistance rates continue to rise worldwide, omadacycline may offer an alternative PEP or treatment option against inhalation anthrax, including anthrax caused by antibiotic-resistant B. anthracis.
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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.
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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.
Subject(s)
Anthrax , Farmers , Health Knowledge, Attitudes, Practice , Livestock , Anthrax/veterinary , Anthrax/epidemiology , Anthrax/prevention & control , Male , Cross-Sectional Studies , Kazakhstan/epidemiology , Female , Humans , Animals , Adult , Farmers/psychology , Farmers/statistics & numerical data , Middle Aged , Young Adult , Zoonoses , Aged , Animal Husbandry/methods , AdolescentABSTRACT
Priestia is a genus that was renamed from the genus Bacillus based on the conserved signature indels (CSIs) in protein sequences that separate Priestia species from Bacillus, with the latter only including species closely related to B. subtilis and B. cereus. Diagnosis of anthrax, a zoonotic disease, is implicated by tripartite anthrax virulence genes (lef, pagA, and cya) and poly-γ-D-glutamic acid capsular genes cap-ABCDE of Bacillus anthracis. Due to the amplification of anthrax virulence genes in Priestia isolates, the search for homologous anthrax virulence genes within the Priestia genomes (n = 9) isolated from animal blood smears was embarked upon through whole genome sequencing. In silico taxonomic identification of the isolates was conducted using genome taxonomy database (GTDB), average nucleotide identity (ANI), and multi-locus sequence typing (MLST), which identified the genomes as P. aryabhattai (n = 5), P. endophytica (n = 2) and P. megaterium (n = 2). A pan-genome analysis was further conducted on the Priestia genomes, including the screening of virulence, antibiotic resistance genes and mobile genetic elements on the sequenced genomes. The oligoribonuclease NrnB protein sequences showed that Priestia spp. possess a unique CSI that is absent in other Bacillus species. Furthermore, the CSI in P. endophytica is unique from other Priestia spp. Pan-genomic analysis indicates that P. endophytica clusters separately from P. aryabhattai and P. megaterium. In silico BLASTn genome analysis using the SYBR primers, Taqman probes and primers that target the chromosomal marker (Ba-1), protective antigen (pagA), and lethal factor (lef) on B. anthracis, showed partial binding to Priestia regions encoding for hypothetical proteins, pyridoxine biosynthesis, hydrolase, and inhibitory proteins. The antibiotic resistance genes (ARG) profile of Priestia spp. showed that the genomes contained no more than two ARGs. This included genes conferring resistance to rifamycin and fosfomycin on P. endophytica, as well as clindamycin on P. aryabhattai and P. megaterium. Priestia genomes lacked B. anthracis plasmids and consisted of plasmid replicon types with unknown functions. Furthermore, the amplification of Priestia strains may result in false positives when qPCR is used to detect the virulence genes of B. anthracis in soil, blood smears, and/or environmental samples.
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Anthrax is a zoonotic bacterial disease caused by Bacillus anthracis. It poses significant threat to humans through contact with infected animals or their by-products. Concerns arise from its long-lasting spore viability and lethality, fuelling its biowarfare potential. Recent anthrax outbreaks across multiple African nations prompted this bibliometric study. The aim of the study was to assess the contributions of African countries, institutions, authors, research funding, and collaborations, while identifying research trends and gaps. We conducted an extensive bibliometric analysis of anthrax-related research publications in Africa from 1923 to 2023, utilizing the Scopus database and VOSviewer. The study covered 364 publications from 32 African countries, accumulating 5,636 citations at an average of 15.5 citations per article, with research articles comprising 88.5% of the corpus. The publication growth rate from 1923 to 2023 was modest at 8.3%, indicating gradual advancement. Notably, there was a significant surge in publications between 2011 and 2023, accounting for 73.1% of total publications. The African research contributions, were categorized into five thematic focuses: ecological dynamics and host interactions, human-livestock anthrax interface, molecular insights into bacterial activity and treatment strategies, collaborative approaches for zoonotic disease prevention, and antibody response and vaccination strategies. Leading institutional contributors included the University of Pretoria and the University of KwaZulu-Natal. Collaborations extended globally to 35 non-African countries, with significant involvement from the United States, United Kingdom, and Germany. Strong African partnerships, especially between Kenya, Nigeria, and South Africa, emerged. The top 10 cited papers explored diverse aspects, including disease impact on wildlife and innovative control strategies, underscoring the importance of multidisciplinary approaches. South Africa played a prominent role, contributing 95 publications and securing funding from various sources, including the National Research Foundation. Collaborations with global institutions highlighted its commitment. This study unveils the dynamic landscape of anthrax research in Africa, emphasizing the pivotal role of collaboration, multidisciplinary One Health approaches, and global partnerships in enhancing research outcomes. Ongoing research and practical solutions for human and animal health remain imperative.
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To enhance the cellular uptake of liposomes, we prepared conventional liposomes with targeting molecules and surface-charged liposomes and evaluated their potential as nano-carriers and vaccine adjuvants by comparing their endocytosis efficiencies using immune cells. Surface-charged liposomes were synthesized via a one-step microfluidic method, which provided a novel, simple, fast, and highly reproducible method for preparing liposomes. Flow cytometry revealed that cationic polyelectrolyte-coated liposomes exhibited higher endocytosis efficiencies (of up to a factor of 100) in A774A.1 cells and JAWs II cells compared with uncoated liposomes or those coated with anionic polyelectrolytes. Positively charged liposomes exhibited some cytotoxicity at quaternary-chitosan coating concentrations higher than 6â¯mg/mL; however, significantly lower cytotoxicities (by a factor of almost ten) were obtained by protein mixing. Furthermore, BALB/c mice vaccinated with a mixture of Anthrax vaccine adsorbed (AVA) and quaternary chitosan-coated liposomes showed faster and stronger anti-PA IgG inductions compared to those vaccinated with AVA alone, with titers positively correlating with the amount of cationic liposome used. This finding clearly reveals that quaternary chitosan-coated liposomes act as both nano-carriers and vaccine adjuvants that significantly enhance in-vivo immune responses to vaccines with low immunogenicities.
Subject(s)
Endocytosis , Liposomes , Mice, Inbred BALB C , Liposomes/chemistry , Animals , Endocytosis/drug effects , Mice , Polyelectrolytes/chemistry , Chitosan/chemistry , Microfluidics/methods , FemaleABSTRACT
Inhalation anthrax is the most severe form of Bacillus anthracis infection, often progressing to fatal conditions if left untreated. While recommended antibiotics can effectively treat anthrax when promptly administered, strains engineered for antibiotic resistance could render these drugs ineffective. Telavancin, a semisynthetic lipoglycopeptide antibiotic, was evaluated in this study as a novel therapeutic against anthrax disease. Specifically, the aims were to (i) assess in vitro potency of telavancin against 17 B. anthracis isolates by minimum inhibitory concentration (MIC) testing and (ii) evaluate protective efficacy in rabbits infected with a lethal dose of aerosolized anthrax spores and treated with human-equivalent intravenous telavancin doses (30 mg/kg every 12 hours) for 5 days post-antigen detection versus a humanized dose of levofloxacin and vehicle control. Blood samples were collected at various times post-infection to assess the level of bacteremia and antibody production, and tissues were collected to determine bacterial load. The animals' body temperatures were also recorded. Telavancin demonstrated potent bactericidal activity against all strains tested (MICs 0.06-0.125 µg/mL). Further, telavancin conveyed 100% survival in this model and cleared B. anthracis from the bloodstream and organ tissues more effectively than a humanized dose of levofloxacin. Collectively, the low MICs against all strains tested and rapid bactericidal in vivo activity demonstrate that telavancin has the potential to be an effective alternative for the treatment or prophylaxis of anthrax infection.
Subject(s)
Aminoglycosides , Anthrax , Anti-Bacterial Agents , Bacillus anthracis , Lipoglycopeptides , Microbial Sensitivity Tests , Respiratory Tract Infections , Animals , Lipoglycopeptides/pharmacology , Rabbits , Anthrax/drug therapy , Anthrax/microbiology , Anthrax/mortality , Bacillus anthracis/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Aminoglycosides/pharmacology , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology , Disease Models, Animal , Levofloxacin/pharmacology , FemaleABSTRACT
(1) Background: Cutaneous anthrax is a disease caused by a Gram-positive bacillus, spore-forming Bacillus anthracis (BA). Cutaneous anthrax accounts for 95% of all anthrax cases, with mortality between 10-40% in untreated forms. The most feared complication, which can be life-threatening and is rarely encountered and described in the literature, is compartment syndrome. (2) Methods: We report a series of six cases of cutaneous anthrax from the same endemic area. In two of the cases, the disease was complicated by compartment syndrome. The systematic review was conducted according to systematic review guidelines, and the PubMed, Google Scholar, and Web of Science databases were searched for publications from 1 January 2008 to 31 December 2023. The keywords used were: "cutaneous anthrax" and "compartment syndrome by cutaneous anthrax". (3) Results: For compartment syndrome, emergency surgical intervention for decompression was required, along with another three surgeries, with hospitalization between 21 and 23 days. In the systematic review, among the 37 articles, 29 did not contain cases focusing on compartment syndrome of the thoracic limb in cutaneous anthrax. The results were included in a Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram. (4) Conclusions: Early recognition of the characteristic cutaneous lesions and compartment syndrome with early initiation of antibiotics and urgent surgical treatment is the lifesaving solution.
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BACKGROUND: Zoonoses are infectious diseases that are transmitted from animals to humans. Studying the knowledge, perceptions and practices of communities related to zoonoses and the associated risk factors is crucial for effective control and prevention. This study aimed to assess the knowledge, perceptions, and practices of respondents on zoonoses and the associated risk factors in and around Chiro town, Ethiopia. Zoonotic diseases, such as rabies, anthrax, bovine tuberculosis, and brucellosis, pose a direct threat to health and livelihoods in the communities where they occur. These diseases emerge due to a combination of human-animal interactions, migration, and contact with wildlife and their respective parasites and vectors. Hence, recognizing residents' perceptions, knowledge, and practices is crucial for effectively minimizing risks. METHODS: A cross-sectional study was conducted from January 2020 to July 2021 in and around Chiro town using a pretested close-ended questionnaire. A total of 350 respondents were selected using simple random sampling methods. The questionnaire included information on the sociodemographic status of the respondents and questions concerning the knowledge, perceptions, and practices of the participants regarding the selected zoonotic diseases. The associations of knowledge, perceptions, and practices related to zoonoses with zoonotic risk factors were analysed using chi-square tests. RESULTS: The study revealed that 82.9% of the respondents had knowledge of bovine tuberculosis, followed by knowledge of rabies (80%), knowledge of anthrax (45.1%), and knowledge of brucellosis (24.3%). Males had greater knowledge of bovine tuberculosis (84.8%), followed by rabies (79.8%) and anthrax (48.6%), while females had greater knowledge of brucellosis (23.6%). The most cited source of information was radio (68%). Most respondents mentioned the outbreaks of rabies (62.5%), bovine tuberculosis (53.2%), anthrax (35.6%), and brucellosis (15.7%). Respondents with higher educational levels and urban residents had more knowledge of zoonoses. More than 75% of respondents had a good perception of the transmission of zoonotic disease from animals, and the practice of consuming raw milk or raw/undercooked meat and sharing the same house with animals was high. CONCLUSION: The majority of respondents reported that they had knowledge of bovine tuberculosis and rabies, but lower knowledge and perceptions were reported for anthrax and brucellosis. These findings illustrate the need for collaboration among animal, human and environmental health offices in one health approach to prevent and control zoonotic disease.
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This review gathers all, to the best of our current knowledge, known lysins, mainly bacteriophage-derived, that have demonstrated activity against Bacillus anthracis strains. B. anthracis is a spore-forming, toxin-producing bacteria, naturally dwelling in soil. It is best known as a potential biowarfare threat, an etiological agent of anthrax, and a severe zoonotic disease. Anthrax can be treated with antibiotics (ciprofloxacin, penicillin, doxycycline); however, their administration may take up even to 60 days, and different factors can compromise their effectiveness. Bacterial viruses, bacteriophages (phages), are natural enemies of bacteria and use their lytic enzymes, endolysins (lysins), to specifically kill bacterial cells. Harnessing the potential of lysins to combat bacterial infections holds promise for diminishing antibiotic usage and, consequently, addressing the escalating antibiotic resistance in bacteria. In this context, we list the lysins with the activity against B. anthracis, providing a summary of their lytic properties in vitro and the outcomes observed in animal models. Bacillus cereus strain ATCC 4342/RSVF1, a surrogate for B. anthracis, was also included as a target bacteria. KEY POINTS: ⢠More than a dozen different B. anthracis lysins have been identified and studied. ⢠They fall into three blocks regarding their amino acid sequence similarity and most of them are amidases. ⢠Lysins could be used in treating B. anthracis infections.
Subject(s)
Anthrax , Anti-Bacterial Agents , Bacillus anthracis , Endopeptidases , Bacillus anthracis/drug effects , Bacillus anthracis/virology , Anthrax/drug therapy , Anthrax/microbiology , Animals , Endopeptidases/pharmacology , Endopeptidases/metabolism , Endopeptidases/genetics , Anti-Bacterial Agents/pharmacology , Bacteriophages/genetics , Bacillus cereus/drug effects , Bacillus cereus/virology , Humans , Bacillus Phages/geneticsABSTRACT
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.
Subject(s)
Animals, Wild , Anthrax , Bacillus anthracis , Animals , Anthrax/epidemiology , Anthrax/veterinary , Anthrax/prevention & control , Bacillus anthracis/isolation & purification , Animals, Wild/microbiology , Ethiopia/epidemiology , Conservation of Natural Resources , EcosystemABSTRACT
We report on a highly significant, positive association between anthrax vaccination and occurrence of Gulf War Illness (GWI) in 111 Gulf War veterans (42 with GWI and 69 controls). GWI was diagnosed in 47.1% of vaccinated veterans but only in 17.2% of non-vaccinated veterans (Pearson χ2 = 7.08, p = 0.008; odds ratio = 3.947; relative risk = 2.617), with 1.6x higher GWI symptom severity in vaccinated veterans (p = 0.007, F-test in analysis of covariance). Next, we tested the hypothesis that the susceptibility to GWI following anthrax vaccination could be due to inability to make antibodies against the anthrax protective antigen (PA), the key protein contained in the vaccine. Since the first step in initiating antibody production would be the binding of PA peptide fragments (typically 15-amino acid long [15-mer]) to peptide-binding motifs of human leukocyte antigen (HLA) Class II molecules, we assessed the binding-motif affinities of such HLA specific molecules to all linear 15-mer peptide fragments of the anthrax PA. We identified a total of 58 HLA Class II alleles carried by the veterans in our sample and found that, of those, 18 (31%) were present in the vaccinated group that did not develop GWI but were absent from the vaccinated group who developed GWI. Remarkably, in silico analyses revealed very high binding affinities of peptide-binding motifs of those 18 HLA alleles with fragments of anthrax vaccine PA, leading to the successful production of anti-PA antibodies. Conversely, the absence of these protective HLA alleles points to a reduced ability to develop antibodies against PA, thus resulting in harmful PA persistence and development of GWI.
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The Gram-positive bacterium Bacillus anthracis is the causative agent of anthrax and a bioterrorism threat worldwide. As a crucial second messenger in many bacterial species, cyclic di-AMP (c-di-AMP) modulates various key processes for bacterial homeostasis and pathogenesis. Overaccumulation of c-di-AMP alters cellular growth and reduces anthrax toxin expression as well as virulence in Bacillus anthracis by unresolved underlying mechanisms. In this report, we discovered that c-di-AMP binds to a series of receptors involved in potassium uptake in B. anthracis. By analyzing Kdp and Ktr mutants for osmotic stress, gene expression, and anthrax toxin expression, we also showed that c-di-AMP inhibits Kdp operon expression through binding to the KdpD and ydaO riboswitch; up-regulating intracellular potassium promotes anthrax toxin expression in c-di-AMP accumulated B. anthracis. Decreased anthrax toxin expression at high c-di-AMP occurs through the inhibition of potassium uptake. Understanding the molecular basis of how potassium uptake affects anthrax toxin has the potential to provide new insight into the control of B. anthracis.IMPORTANCEThe bacterial second messenger cyclic di-AMP (c-di-AMP) is a conserved global regulator of potassium homeostasis. How c-di-AMP regulates bacterial virulence is unknown. With this study, we provide a link between potassium uptake and anthrax toxin expression in Bacillus anthracis. c-di-AMP accumulation might inhibit anthrax toxin expression by suppressing potassium uptake.
Subject(s)
Antigens, Bacterial , Bacillus anthracis , Bacterial Proteins , Bacterial Toxins , Dinucleoside Phosphates , Gene Expression Regulation, Bacterial , Potassium , Bacillus anthracis/metabolism , Bacillus anthracis/genetics , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Potassium/metabolism , Antigens, Bacterial/metabolism , Antigens, Bacterial/genetics , Bacterial Toxins/metabolism , Bacterial Toxins/genetics , Dinucleoside Phosphates/metabolism , Virulence/genetics , Down-Regulation , Anthrax/microbiology , Anthrax/metabolism , Riboswitch/genetics , Operon , Protein KinasesABSTRACT
Anthrax is a rare zoonotic disease in humans caused by Bacillus anthracis. The most common form of this disease is cutaneous anthrax. Rarely, eye involvement may occur. In this case, a nine-year-old male patient with anthrax on his left eyelids is presented. From the patient's history, it was learned that a slight papular reaction occurred on the left side of the eye, then the lesion enlarged within three days, and edema developed around the eye. On the fifth day of the patient's preseptal cellulitis diagnosis, progress in eye lesions and necrosis and eschar formation around the eyes were detected, while Bacillus anthracis polymerase chain reaction (PCR) positivity was detected on the fifth day of the patient's complaints. The patient was treated with ciprofloxacin and clindamycin and a clinical response was achieved. Anthrax should be kept in mind in the differential diagnosis of preseptal and orbital cellulitis, especially in patients who have close contact with animals. If palpebral anthrax is not treated effectively on time, it can leave scars on the eyelids and cause permanent deformities and loss of function. Early diagnosis and initiation of antibiotic therapy significantly reduce the occurrence of complications. In this case report, a pediatric case with eyelid anthrax, which is rarely seen in anthrax disease, is presented.
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Anthrax remains a threat, especially in countries like Kyrgyzstan with developed livestock farming. Despite preventive efforts, sporadic outbreaks endure on an annual basis, transmitted from infected animals to humans. Here, we report a severe anthrax case in an 8-month-old child known to be caused when a sick calf was slaughtered in the neighborhood without proper protocols, resulting in intra-family infection. This underscores the importance of swift diagnosis, treatment, preventive measures, and awareness of zoonotic infections, animal vaccination and adherence to sanitary and veterinary protocols.
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During World War I (WWI), also referred to as 'The Great War,' Germany implemented a pioneering biowarfare program as part of a broader military strategy to undermine Allied forces by targeting their logistical and supply capabilities. This initiative, unprecedented in its systematic and strategic application, utilized a variety of pathogens, primarily targeting animal populations, to disrupt support systems without contravening international laws, specifically the 1907 Hague Convention. The operations, shrouded in secrecy and largely led by the German General Staff, included sophisticated sabotage actions against both enemy and neutral states. The allegations and usage of bioweapons increased the interest of the Great Powers in further developing their own biowarfare program.
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This article considers ethical considerations surrounding pediatric vaccine development for pandemic preparedness, examines some historical cases of pediatric vaccines developed during past smallpox, influenza, and 2019 coronavirus disease pandemics, and discusses the current state of vaccine development for pandemic preparedness, including vaccines against smallpox/mpox, influenza, anthrax, and Ebola that are included in the US Strategic National Stockpile and vaccines being developed against priority pathogens identified by the World Health Organization.
Subject(s)
Vaccine Development , Humans , Child , Pandemics/prevention & control , COVID-19/prevention & control , COVID-19/epidemiology , Vaccines , United StatesABSTRACT
Mammary tumors are the most frequent type of neoplasms in intact female dogs. New therapies that target neoplastic cells without affecting normal cells are highly sought. The Bacillus anthracis toxin has been reengineered to target tumor cells that express urokinase plasminogen activators and metalloproteinases. In previous studies carried out in our laboratory, the reengineered anthrax toxin had inhibitory effects on canine oral mucosal melanoma and canine osteosarcoma cells. In this study, five canine neoplastic epithelial cell lines (four adenocarcinomas and one adenoma) and one non-neoplastic canine mammary epithelial cell line were treated with different concentrations of reengineered anthrax toxin components. Cell viability was quantified using an MTT assay and half-maximal inhibitory concentration (IC50) values. Cell lines were considered sensitive when the IC50 was lower than 5000 ng/ml. One canine mammary adenocarcinoma cell line and one mammary adenoma cell line showed significantly decreased viability after treatment, whereas the non-neoplastic cell line was resistant. We conclude that the reengineered anthrax toxin may be considered a targeted therapy for canine mammary neoplasms while preserving normal canine mammary epithelial cells.
Subject(s)
Antigens, Bacterial , Bacterial Toxins , Dog Diseases , Mammary Neoplasms, Animal , Animals , Dogs , Mammary Neoplasms, Animal/drug therapy , Bacterial Toxins/pharmacology , Female , Antigens, Bacterial/pharmacology , Cell Line, Tumor , Dog Diseases/drug therapy , Epithelial Cells/drug effects , Adenocarcinoma/veterinary , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Cell Survival/drug effects , Adenoma/veterinary , Adenoma/drug therapy , Adenoma/pathologyABSTRACT
The metagenomic next-generation sequencing (mNGS) method is preferred for genotyping useful for the identification of organisms, illumination of metabolic pathways, and determination of microbiota. It can accurately obtain all the nucleic acid information in the test sample. Anthrax is one of the most important zoonotic diseases, infecting mainly herbivores and occasionally humans. The disease has four typical clinical forms, cutaneous, gastrointestinal, inhalation, and injection, all of which may result in sepsis or meningitis, with cutaneous being the most common form. Here, we report a case of cutaneous anthrax diagnosed by mNGS in a butcher. Histopathology of a skin biopsy revealed PAS-positive bacilli. Formalin-fixed paraffin-embedded (FFPE) tissue sample was confirmed the diagnosis of anthrax by mNGS. He was cured with intravenous penicillin. To our knowledge, this is the first case of cutaneous anthrax diagnosed by mNGS using FFPE tissue. mNGS is useful for identifying pathogens that are difficult to diagnose with conventional methods, and FFPE samples are simple to manage. Compared with traditional bacterial culture, which is difficult to cultivate and takes a long time, mNGS can quickly and accurately help us diagnose anthrax, so that anthrax can be controlled in a timely manner and prevent the outbreak of epidemic events.
Subject(s)
Anthrax , Skin Diseases, Bacterial , Male , Humans , Anthrax/diagnosis , Paraffin Embedding , Formaldehyde/therapeutic use , High-Throughput Nucleotide Sequencing/methods , Metagenomics/methods , Sensitivity and SpecificityABSTRACT
Background: This study was to compare a baseline and endline survey which were conducted to assess the changes in knowledge, attitude and practices about anthrax disease among the communities after One Health intervention for the elimination of human anthrax in an endemic district of Odisha. Methods: A total of 2670 respondents were interviewed during the baseline and 2511 for the endline survey using a structured questionnaire by multi-stage sampling method. Descriptive statistics were used and logistic regression was performed to estimate the relationship between the variables and knowledge of anthrax. Results: Out of the total participants in the study, males were about 76.25% in baseline and 72.08% in endline and about half of the total respondents were illiterate. Majority of the respondents had reported agriculture as their main occupation during both surveys. More than 50% of the respondents had livestock in their houses and farming was the main purpose for keeping them in both surveys. Around 20.26% of respondents knew about anthrax in baseline which raised to 53.64% after One Health intervention. Almost 21.29% of livestock owners had vaccinated their animals against anthrax disease throughout baseline, which increased to 66.5% during the endline survey. Conclusion: This study highlights a significant surge in both knowledge and practices related to anthrax within the community after the implementation of intervention packages based on the One Health approach. The outcome of our study signified the importance of One Health interventions to address the health challenges related to zoonotic diseases in tribal communities. The data could be useful for local Governments to incorporate such an approach in their health policy to eliminate human anthrax.