Search Results (13)

Sheep and goats are an important source of livelihood for smallholder farmers in sub-Saharan Africa (SSA). These livestock are almost entirely managed by resource-poor, smallholder farmers and pastoralists. Despite the large number of sheep and goats in SSA, their productivity is low, mainly due to diseases, poor feed, and inferior breeds. This review aims to summarize the most important diseases in small ruminants in SSA, with a focus on current treatment and control strategies. The following diseases were identified as the most significant constraints for small ruminant farmers: helminthoses, including gastrointestinal nematode infestation, lungworm infestation, fasciolosis, and cerebral coenurosis; viral diseases, such as peste des petits ruminants (PPR), sheep and goat pox, and contagious ecthyma (orf); bacterial diseases, including contagious caprine pleuropneumonia (CCPP), pneumonic pasteurellosis, and anthrax; as well as ectoparasite infestations. The diseases have significant economic implications due to mortality and production losses. Depending on the disease, they may also impact trade and export and hinder the introduction of new, more productive breeds. The ability to control diseases more efficiently is often limited due to financial constraints. In the case of infection with internal parasites, a lack of knowledge about the epidemiology of the disease, as well as the availability of appropriate anthelmintics and the development of resistance against commonly used anthelmintics, are often barriers. The control of viral diseases depends on the accessibility, quality, and handling of vaccines, whereas in bacterial diseases, increasing antibiotic resistance and inappropriate antimicrobial treatments pose challenges, as well as the availability of appropriate vaccines and their use. In the case of ectoparasitic infections, a strategic, regular, and appropriate antiparasitic treatment approach is often not achieved. Full article

Bacillus anthracis is a deadly pathogen that under unfavourable conditions forms highly resistant spores which enable them to survive for a long period of time. Spores of B. anthracis are transmitted through the contaminated soil or animal products and enter to the host through the skin, lungs or oral route and can cause cutaneous, injection, inhalation and gastrointestinal anthrax, respectively. The disease is caused by the toxin which is produced by them once they germinate within the host cell. Anthrax toxin is the major virulence factor which has the ability to kill the host cell. The role of protein kinases and phosphatases of B. anthracis in toxin production and other virulence related properties have also been reported. There are two vaccines, BioThrax and CYFENDUS^TM, which are approved by the FDA-USA to prevent anthrax disease. Recently, anthrax toxin has also been shown to be a potential candidate for cancer therapeutics. Through present review, we aim to provide insights into sporulation, transmission and pathogenesis of B. anthracis as well as the current state of its prevention, treatment, vaccines and possible therapeutic uses in cancer. Full article

Bacillus anthracis is the bacterium responsible for causing the zoonotic disease called anthrax. The disease presents itself in different forms like gastrointestinal, inhalation, and cutaneous. Bacterial spores are tremendously adaptable, can persist for extended periods and occasionally endanger human health. The Anthrax Toxin Receptor-2 (ANTXR2) gene acts as membrane receptor and facilitates the entry of the anthrax toxin into host cells. Additionally, mutations in the ANTXR2 gene have been linked to various autoimmune diseases, including Hyaline Fibromatosis Syndrome (HFS), Ankylosing Spondylitis (AS), Juvenile Hyaline Fibromatosis (JHF), and Infantile Systemic Hyalinosis (ISH). This study delves into the genetic landscape of ANTXR2, aiming to comprehend its associations with diverse disorders, elucidate the impacts of its mutations, and pinpoint minimal non-pathogenic mutations capable of reducing the binding affinity of the ANTXR2 gene with the protective antigen. Recognizing the pivotal role of single-nucleotide polymorphisms (SNPs) in shaping genetic diversity, we conducted computational analyses to discern highly deleterious and tolerated non-synonymous SNPs (nsSNPs) in the ANTXR2 gene. The Mutpred2 server determined that the Arg465Trp alteration in the ANTXR2 gene leads to altered DNA binding (p = 0.22) with a probability of a deleterious mutation of 0.808; notably, among the identified deleterious SNPs, rs368288611 (Arg465Trp) stands out due to its significant impact on altering the DNA-binding ability of ANTXR2. We propose these SNPs as potential candidates for hypertension linked to the ANTXR2 gene, which is implicated in blood pressure regulation. Noteworthy among the tolerated substitutions is rs200536829 (Ala33Ser), recognized as less pathogenic; this highlights its potential as a valuable biomarker, potentially reducing side effects on the host while also reducing binding with the protective antigen protein. Investigating these SNPs holds the potential to correlate with several autoimmune disorders and mitigate the impact of anthrax disease in humans. Full article

Environmental contamination with Bacillus anthracis spores poses uncertain threats to human health. We undertook a study to determine whether inhabitants of the anthrax-endemic region of Kars in eastern Türkiye could develop immune responses to anthrax toxins without recognised clinical infection. We measured anti-PA and anti-LF IgG antibody concentrations by ELISA in serum from 279 volunteers, 105 of whom had previously diagnosed anthrax infection (100 cutaneous, 5 gastrointestinal). Of the 174 without history of infection, 72 had prior contact with anthrax-contaminated material. Individuals were classified according to demographic parameters, daily working environment, and residence type. All villages in this study had recorded previous animal or human anthrax cases. Stepwise regression analyses showed that prior clinical infection correlated strongly with concentrations at the upper end of the ranges observed for both antibodies. For anti-PA, being a butcher and duration of continuous exposure risk correlated with high concentrations, while being a veterinarian or shepherd, time since infection, and town residence correlated with low concentrations. For anti-LF, village residence correlated with high concentrations, while infection limited to fingers or thumbs correlated with low concentrations. Linear discriminant analysis identified antibody concentration profiles associated with known prior infection. Profiles least typical of prior infection were observed in urban dwellers with known previous infection and in veterinarians without history of infection. Four individuals without history of infection (two butchers, two rural dwellers) had profiles suggesting unrecognised prior infection. Healthy humans therefore appear able to tolerate low-level exposure to environmental B. anthracis spores without ill effect, but it remains to be determined whether this exposure is protective. These findings have implications for authorities tasked with reducing the risk posed to human health by spore-contaminated materials and environments. Full article

Anthrax is one of the most important zoonotic diseases which primarily infects herbivores and occasionally humans. The etiological agent is Bacillus anthracis which is a Gram-positive, aerobic, spore-forming, nonmotile, rod-shaped bacillus. The spores are resistant to environmental conditions and remain viable for a long time in contaminated soil, which is the main reservoir for wild and domestic mammals. Infections still occur in low-income countries where they cause suffering and economic hardship. Humans are infected by contact with ill or dead animals, contaminated animal products, directly exposed to the spores in the environment or spores released as a consequence of a bioterrorist event. Three classical clinical forms of the disease, cutaneous, gastrointestinal and inhalation, are seen, all of which can potentially lead to sepsis or meningitis. A new clinical form in drug users has been described recently and named “injectional anthrax” with high mortality (>33%). The symptoms of anthrax in the early stage mimics many diseases and as a consequence it is important to confirm the diagnosis using a bacterial culture or a molecular test. With regards to treatment, human isolates are generally susceptible to most antibiotics with penicillin G and amoxicillin as the first choice, and ciprofloxacin and doxycycline serving as alternatives. A combination of one or more antibiotics is suggested in systemic anthrax. Controlling anthrax in humans depends primarily on effective control of the disease in animals. Spore vaccines are used in veterinary service, and an acellular vaccine is available for humans but its use is limited. Full article

North America is a large producer of beef and contains approximately 12% of the world’s cattle inventory. Feedlots are an integral part of modern cattle production in North America, producing a high-quality, wholesome protein food for humans. Cattle, during their final stage, are fed readily digestible high-energy density rations in feedlots. Cattle in feedlots are susceptible to certain zoonotic diseases that impact cattle health, growth performance, and carcass characteristics, as well as human health. Diseases are often transferred amongst pen-mates, but they can also originate from the environment and be spread by vectors or fomites. Pathogen carriage in the gastrointestinal tract of cattle often leads to direct or indirect contamination of foods and the feedlot environment. This leads to the recirculation of these pathogens that have fecal–oral transmission within a feedlot cattle population for an extended time. Salmonella, Shiga toxin-producing Escherichia coli, and Campylobacter are commonly associated with animal-derived foods and can be transferred to humans through several routes such as contact with infected cattle and the consumption of contaminated meat. Brucellosis, anthrax, and leptospirosis, significant but neglected zoonotic diseases with debilitating impacts on human and animal health, are also discussed. Full article

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. Full article

Hyaline fibromatosis syndrome (HFS), resulting from ANTXR2 mutations, is an ultra-rare disease that causes intestinal lymphangiectasia and protein-losing enteropathy (PLE). The mechanisms leading to the gastrointestinal phenotype in these patients are not well defined. We present two patients with congenital diarrhea, severe PLE and unique clinical features resulting from deleterious ANTXR2 mutations. Intestinal organoids were generated from one of the patients, along with CRISPR-Cas9 ANTXR2 knockout, and compared with organoids from two healthy controls. The ANTXR2-deficient organoids displayed normal growth and polarity, compared to controls. Using an anthrax-toxin assay we showed that the c.155C>T mutation causes loss-of-function of ANTXR2 protein. An intrinsic defect of monolayer formation in patient-derived or ANTXR2^KO organoids was not apparent, suggesting normal epithelial function. However, electron microscopy and second harmonic generation imaging showed abnormal collagen deposition in duodenal samples of these patients. Specifically, collagen VI, which is known to bind ANTXR2, was highly expressed in the duodenum of these patients. In conclusion, despite resistance to anthrax-toxin, epithelial cell function, and specifically monolayer formation, is intact in patients with HFS. Nevertheless, loss of ANTXR2-mediated signaling leads to collagen VI accumulation in the duodenum and abnormal extracellular matrix composition, which likely plays a role in development of PLE. Full article

Bacillus anthracis has been identified as a potential military and bioterror agent as it is relatively simple to produce, with spores that are highly resilient to degradation in the environment and easily dispersed. These characteristics are important in describing how anthrax could be used as a weapon, but they are also important in understanding and determining appropriate prevention and treatment of anthrax disease. Today, anthrax disease is primarily enzootic and found mostly in the developing world, where it is still associated with considerable mortality and morbidity in humans and livestock. This review article describes the spectrum of disease caused by anthrax and the various prevention and treatment options. Specifically we discuss the following; (1) clinical manifestations of anthrax disease (cutaneous, gastrointestinal, inhalational and intravenous-associated); (2) immunology of the disease; (3) an overview of animal models used in research; (4) the current World Health Organization and U.S. Government guidelines for investigation, management, and prophylaxis; (5) unique regulatory approaches to licensure and approval of anthrax medical countermeasures; (6) the history of vaccination and pre-exposure prophylaxis; (7) post-exposure prophylaxis and disease management; (8) treatment of symptomatic disease through the use of antibiotics and hyperimmune or monoclonal antibody-based antitoxin therapies; and (9) the current landscape of next-generation product candidates under development. Full article

The probiotic yeast Saccharomyces boulardii (S. boulardii) has been prescribed for the prophylaxis and treatment of several infectious diarrheal diseases. Gastrointestinal anthrax causes fatal systemic disease. In the present study, we investigated the protective effects conferred by Saccharomyces boulardii CNCM I-745 strain on polarized T84 columnar epithelial cells intoxicated by the lethal toxin (LT) of Bacillus anthracis. Exposure of polarized T84 cells to LT affected cell monolayer integrity, modified the morphology of tight junctions and induced the formation of actin stress fibers. Overnight treatment of cells with S. boulardii before incubation with LT maintained the integrity of the monolayers, prevented morphological modification of tight junctions, restricted the effects of LT on actin remodeling and delayed LT-induced MEK-2 cleavage. Mechanistically, we demonstrated that in the presence of S. boulardii, the medium is depleted of both LF and PA sub-units of LT and the appearance of a cleaved form of PA. Our study highlights the potential of the S. boulardii CNCM I-745 strain as a prophylactic agent against the gastrointestinal form of anthrax. Full article

The principal portal for anthrax infection in natural animal outbreaks is the digestive tract. Enteric exposure to anthrax, which is difficult to detect or prevent in a timely manner, could be exploited as an act of terror through contamination of human or animal food. Our group has developed a novel animal model of gastrointestinal (GI) anthrax for evaluation of disease pathogenesis and experimental therapeutics, utilizing vegetative Bacillus anthracis (Sterne strain) administered to A/J mice (a complement-deficient strain) by oral gavage. We hypothesized that a humanized recombinant monoclonal antibody (mAb) * that neutralizes the protective antigen (PA) component of B. anthracis lethal toxin (LT) and edema toxin (ET) could be an effective treatment. Although the efficacy of this anti-anthrax PA mAb has been shown in animal models of inhalational anthrax, its activity in GI infection had not yet been ascertained. We hereby demonstrate that passive immunotherapy with anti-anthrax PA mAb, administered at the same time as gastrointestinal exposure to B. anthracis, prevents lethal sepsis in nearly all cases (>90%), while a delay of up to forty-eight hours in treatment still greatly reduces mortality following exposure (65%). Moreover, passive immunotherapy protects against enteric invasion, associated mucosal injury and subsequent dissemination by gastrointestinal B. anthracis, indicating that it acts to prevent the initial stages of infection. * Expired raxibacumab being cycled off the Strategic National Stockpile; biological activity confirmed by in vitro assay. Full article

Ingestion of Bacillus anthracis results in rapid gastrointestinal (GI) infection, known as GI anthrax. We previously showed that during GI anthrax, there is swift deterioration of intestinal barrier function leading to translocation of gut-associated bacteria into systemic circulation. Additionally, we described dysfunction in colonic B cells. In concordance with our previous studies, here, we report early migration of the Sterne strain of B. anthracis along with other gut-resident bacteria into the infected murine liver. Additionally, despite a global decrease in the B cell population, we observed an increase in both B-1a and marginal zone (MZ)-like B cells. Both of these cell types are capable of producing immunoglobulins against common pathogens and commensals, which act as a general antibody barrier before an antigen-specific antibody response. Accumulation of these cells in the liver was associated with an increase in chemokine expression. These data suggest that the presence of Sterne and other commensals in the liver trigger migration of MZ-like B cells from the spleen to the liver to neutralize systemic spread. Further research is required to evaluate the possible cause of their failure to clear the infection within the liver, including the potential role of dysfunctional mitogen-activated protein kinase (MAPK) signaling. Full article

Bioterrorism is one of the main public health categorical domains. According to sociological analytics, in postmodern society terrorism is one of the real threats of the 21st century. While rare, the use of biological weapons has a long history. Recently, anthrax has been evaluated as one of the most dangerous biological weapons. Naturally occurring anthrax in humans is a disease acquired from contact with anthrax-infected animals or anthrax-contaminated animal products. Usually anthrax infection occurs in humans by three major routes: inhalational, cutaneous, and gastrointestinal. Inhalational anthrax is expected to account for most serious morbidity and most mortality. The clinical presentation of inhalation anthrax has been described as a two-stage illness. Many factors contribute to the pathogenesis of Bacillus anthracis. Antibiotics, anthrax globulin, corticosteroids, mechanical ventilation, vaccine are possible tools of therapy. Smallpox existed in two forms: variola major, which accounted for most morbidity and mortality, and a milder form, variola minor. Smallpox spreads from person to person primarily by droplet nuclei or aerosols expelled from the oropharynx of infected persons and by direct contact. In the event of limited outbreak with few cases, patients should be admitted to the hospital and confined to rooms that are under negative pressure and equipped with high-efficiency particulate air filtration. In larger outbreaks, home isolation and care should be the objective for most patients. Progress in detection, suitable vaccines, postexposure prophylaxis, infection control, and decontamination might be serious tools in fight against the most powerful biological weapon. To assure that the public health and healthcare system can respond to emergencies, the government should direct resources to strengthen the emergency-response system, create medication stockpiles, and improve the public health infrastructure. Full article