Form Of Anthrax Research Articles

Aerosolized Intratracheal Inoculation of Recombinant Protective Antigen (rPA) Vaccine Provides Protection Against Inhalational Anthrax in B10.D2-Hc0 Mice.

Anthrax caused by Bacillus anthracis is a fatal zoonotic disease with a high lethality and poor prognosis. Inhalational anthrax is the most severe of the three forms of anthrax. The currently licensed commercial human anthrax vaccines require a complex immunization procedure for efficacy and have side effects that limit its use in emergent situations. Thus, development of a better anthrax vaccine is necessary. In this study, we evaluate the potency and efficacy of aerosolized intratracheal (i.t.) inoculation with recombinant protective antigen (rPA) subunit vaccines against aerosolized B. anthracis Pasteur II spores (an attenuated strain) challenge in a B10.D2-Hc0 mouse (deficient in complement component C5) model. Immunization of rPA in liquid, powder or powder reconstituted formulations via i.t. route conferred 100% protection against a 20× LD50 aerosolized Pasteur II spore challenge in mice, compared with only 50% of subcutaneous (s.c.) injection with liquid rPA. Consistently, i.t. inoculation of rPA vaccines induced a higher lethal toxin (LeTx) neutralizing antibody titer, a stronger lung mucosal immune response and a greater cellular immune response than s.c. injection. Our results demonstrate that immunization with rPA dry powder vaccine via i.t. route may provide a stable and effective strategy to improve currently available anthrax vaccines and B10.D2-Hc0 mice challenged with B. anthracis attenuated strains might be an alternative model for anthrax vaccine candidate screening.

A putative exosporium lipoprotein GBAA0190 of Bacillus anthracis as a potential anthrax vaccine candidate

BackgroundBacillus ancthracis causes cutaneous, pulmonary, or gastrointestinal forms of anthrax. B. anthracis is a pathogenic bacterium that is potentially to be used in bioterrorism because it can be produced in the form of spores. Currently, protective antigen (PA)-based vaccines are being used for the prevention of anthrax, but it is necessary to develop more safe and effective vaccines due to their prolonged immunization schedules and adverse reactions.MethodsWe selected the lipoprotein GBAA0190, a potent inducer of host immune response, present in anthrax spores as a novel potential vaccine candidate. Then, we evaluated its immune-stimulating activity in the bone marrow-derived macrophages (BMDMs) using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Protective efficacy of GBAA0190 was evaluated in the guinea pig (GP) model.ResultsThe recombinant GBAA0190 (r0190) protein induced the expression of various inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1α (MIP-1α) in the BMDMs. These immune responses were mediated through toll-like receptor 1/2 via activation of mitogen-activated protein (MAP) kinase and Nuclear factor-κB (NF-κB) pathways. We demonstrated that not only immunization of r0190 alone, but also combined immunization with r0190 and recombinant PA showed significant protective efficacy against B. anthracis spore challenges in the GP model.ConclusionsOur results suggest that r0190 may be a potential target for anthrax vaccine.

Gambaran Umum, Prevalensi, dan Pencegahan Antraks pada Manusia di Indonesia

Anthrax is a neglected zoonotic disease that remains a global issue because it can cause regular epidemics. Anthrax affects not only health systems but also social-economic conditions, safety, and welfare of the people. This paper aimed to give an overview of human anthrax, prevalence, and prevention in Indonesia. A literature search was performed using search engines such as Google Scholar, Crossref, Mendeley, PLoS One, Elsevier, dan the Ministry of Health official website. The literature used were published between 2015-2020. Anthrax is caused by Bacillus anthracis that affects animals and humans. The virulence factors of these bacteria are determined by the tripartite toxin complex and poly-γ-D-glutamic acid capsule. Anthrax in humans can be found in four forms, namely cutaneous, gastrointestinal, inhalational, and injection anthrax. Each form of anthrax can develop into meningitis and sepsis. Anthrax treatment is commonly done by administering antibiotics. In Indonesia, 14 provinces have been declared anthrax endemic areas. The prevalence of human anthrax in Indonesia is fluctuating and most of it is cutaneous anthrax. Prevention and control of anthrax can be done mainly by vaccination, obeying the rules or standard operating procedures of the authorities, multisectoral cooperation, strengthening anthrax surveillance, increasing resources for diagnosis, increasing public knowledge, and awareness.

THE CURRENT SITUATION ON ANTHRAX IN RUSSIA AND IN THE WORLD. MAIN TRENDS AND FEATURES

The current situation on anthrax is characterized as unstable. Instability is associated with recurring epizootic outbreaks complicated by human anthrax cases, as people contract infection mainly through contact with sick animals, their carcasses or animal products. Mentioned are new aerosol and parenteral ways of anthrax contracting. Parenteral use of contaminated heroin led to emergence of new clinical form of anthrax – injectional. Conception on anthrax agent evolution is replenished by data on pathogenic bacilli strains, that occupy an intermediate position between B. anthracis and B. cereus. Ecology of anthrax microbe is considered in view of its interaction with bacteriophages, rhizosphere and soil microflora. Research related to the environmental characteristics of habitat niches and genotypes of B. anthracis, explaining the geographical distribution of areas with a high risk of disease, may allow to optimize the program of animals immunization, which is the most effective measure for the prevention of anthrax.

The Saccharomyces boulardii CNCM I-745 strain shows protective effects against the B. anthracis LT toxin.

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.

Cutaneous Anthrax in an Unestimated Area of Body

Ertugrul Guclu, Nazan Tuna, Oguz Karabay Anthrax is a zoonotic disease caused by Bacillus anthracis. cutaneous anthrax is the most commonly seen form of anthrax. Skin lesions usually occur on the most exposed areas of the body, such as the face, neck, hand or upper extremity. The aim of this paper is to report a case of cutaneous anthrax form which was occurred on an unexpected area of the body of a slaughter-house worker.

A case of fatal gastrointestinal anthrax in north eastern iran.

Background. Bacillus species are aerobic or facultative anaerobic, gram-positive, or gram-variable spore-forming rods. They are ubiquitous in the environmental sources. Bacillus anthracis may usually cause three forms of anthrax: inhalation, gastrointestinal, and cutaneous. The gastrointestinal (GI) anthrax develops after eating contaminated meat. In this paper we report septic intestinal anthrax. Case Presentation. We report an isolation of Bacillus anthracis from blood culture of patient with intestinal anthrax. Bacillus anthracis was isolated from a blood culture of a 34-year-old man who had a history of severe abdominal pain, bloody diarrhea, nausea, vomiting, fever, sweating, and lethargy within 4 to 5 days after eating the meat of domestic goat. He had evidence of severe infection and septic shock and did not respond to treatments and subsequently expired 9 hours after hospitalization. Conclusion. Gastrointestinal anthrax is characterized by rapid onset, fever, and septicemia. Rapid diagnosis and prompt initiation of antibiotic therapy can help in survival. Most of previous cases of septicemic anthrax were related to injection drug users but, in our case, septicemia occurred after gastrointestinal anthrax.

First Autochthonous Coinfected Anthrax in an Immunocompetent Patient.

Cutaneous anthrax has a mortality rate of 20% if no antibacterial treatment is applied. The clinical manifestations of cutaneous anthrax are obviously striking, but coinfection may produce atypical lesions and mask the clinical manifestations and proper laboratory diagnosis. Anthrax is known to be more common in the Middle East and Iran is one of the countries in which the zoonotic form of anthrax may still be encountered. We report a case of a 19-years-old male who used to apply Venetian ceruse on his skin. Venetian ceruse (also known as Spirits of Saturn) is an old cosmetic product used for skin whitening traditionally made from sheep's spinal cord. The patient referred to the Referral Laboratory, Mazandaran University of Medical Sciences, Sari, Iran, with atypical dermatosis, pronounced pain, and oedema of the affected tissue. It was confirmed by both conventional and molecular analysis that culture was a mixture of Bacillus anthracis and Trichophyton interdigitale. The patient was initially treated with ceftriaxone (1000 mg/day for two weeks), gentamicin (1.5–2 mg/kg/day), terbinafine (200 mg/week for one month), and 1% clotrimazole cream (5 weeks) two times per day which resulted in gradual improvement. No relapse could be detected after one-year follow-up. Anthrax infection might present a broader spectrum of symptoms than expected by clinicians. These unfamiliar characteristics may lead to delayed diagnosis, inadequate treatment, and higher mortality rate. Clinicians need to be aware of this issue in order to have successful management over this infection.

Comparison of survivors and nonsurvivors in 27 confirmed injectional anthrax cases from the 2009 outbreak in Scotland

From December 2009 to December 2010, 47 patients in Scotland presented with confirmed anthrax infection manifested by soft tissue disease related to heroin injection. These cases represent the first known outbreak of a recently recognized form of anthrax, termed injectional anthrax, which appears to be associated with a high mortality rate (28% in confirmed cases from the UK outbreak). While epidemiologic data from this outbreak have been published, no report has systematically described findings in patients at presentation or compared these findings in nonsurvivors and survivors.

Updating Perspectives on the Initiation of Bacillus anthracis Growth and Dissemination through Its Host

Since 1957, it has been proposed that the dissemination of inhalational anthrax required spores to be transported from the lumena of the lungs into the lymphatic system. In 2002, this idea was expanded to state that alveolar macrophages act as a "Trojan horse" capable of transporting spores across the lung epithelium into draining mediastinal lymph nodes. Since then, the Trojan horse model of dissemination has become the most widely cited model of inhalational infection as well as the focus of the majority of studies aiming to understand events initiating inhalational anthrax infections. However, recent observations derived from animal models of Bacillus anthracis infection are inconsistent with aspects of the Trojan horse model and imply that bacterial dissemination patterns during inhalational infection may be more similar to the cutaneous and gastrointestinal forms than previously thought. In light of these studies, it is of significant importance to reassess the mechanisms of inhalational anthrax dissemination, since it is this form of anthrax that is most lethal and of greatest concern when B. anthracis is weaponized. Here we propose a new "jailbreak" model of B. anthracis dissemination which applies to the dissemination of all common manifestations of the disease anthrax. The proposed model impacts the field by deemphasizing the role of host cells as conduits for dissemination and increasing the role of phagocytes as central players in innate defenses, while moving the focus toward interactions between B. anthracis and lymphoid and epithelial tissues.

The Bioterrorist Attacks on America

This article discusses the events surrounding the 9/11 bioterrorist attacks upon US citizens in which anthrax spores were utilized. The arguments presented in this article substantiate the shortcomings regarding the search of “domestic” terrorists, indicating that agents from the Arab world were involved in the organized attacks of sending letters with anthrax spores. Since the attacks employed the use of the weaponized aerosol form of anthrax, there is evidence which demonstrates that the manufacturing of the spores was carried out in a country with capabilities of developing bacteriological weapons. Ultimately, this article presents legitimate arguments in which further investigation is warranted.

Primary Involvement of Pharynx and Peyer's Patch in Inhalational and Intestinal Anthrax

Bacillus anthracis causes three forms of anthrax: inhalational, gastrointestinal, and cutaneous. Anthrax is characterized by both toxemia, which is caused by secretion of immunomodulating toxins (lethal toxin and edema toxin), and septicemia, which is associated with bacterial encapsulation. Here we report that, contrary to the current view of B. anthracis pathogenesis, B. anthracis spores germinate and establish infections at the initial site of inoculation in both inhalational and cutaneous infections without needing to be transported to draining lymph nodes, and that inhaled spores establish initial infection in nasal-associated lymphoid tissues. Furthermore, we found that Peyer's patches in the mouse intestine are the primary site of bacterial growth after intragastric inoculation, thus establishing an animal model of gastrointestinal anthrax. All routes of infection progressed to the draining lymph nodes, spleen, lungs, and ultimately the blood. These discoveries were made possible through the development of a novel dynamic mouse model of B. anthracis infection using bioluminescent non-toxinogenic capsulated bacteria that can be visualized within the mouse in real-time, and demonstrate the value of in vivo imaging in the analysis of B. anthracis infection. Our data imply that previously unrecognized portals of bacterial entry demand more intensive investigation, and will significantly transform the current perception of inhalational, gastrointestinal, and cutaneous B. anthracis pathogenesis.

611. Induction of Persistent Passive Immunity Against Anthrax Toxin by an Adeno-Associated Virus Type rh10 Vector Expressing Anti-Protective Antigen Antibody

The inhalational form of anthrax, a disease caused by infection with Bacillus anthracis, is often fatal and is a serious threat for use in bioterror attacks. The major virulence factors are encoded by the genes for protective antigen (PA), lethal factor (LF), and edema factor. Lethal toxin, comprising PA and LF, is responsible for systemic fatal pathophysiology associated with the B. anthracis infection. Currently available methods of protecting the general civilian population against anthrax are limited. A vaccine based on recombinant PA is being developed and anti-PA (|[alpha]|PA) monoclonal antibodies are being evaluated for induction of passive immunity against B. anthracis. We have previously demonstrated that an adenovirus vector encoding |[alpha]|PA single-chain antibody provided a survival advantage from anthrax lethal toxin challenge (Kasuya et al. Mol. Ther.2005, 11: 237|[ndash]|244). In the present study, we hypothesized that an adeno-associated virus type rh10 vector encoding an |[alpha]|PA (heavy and light chain) full-length antibody would provide a robust, persistent immunotherapy against anthrax toxin. We evaluated the expression of full-length mouse monoclonal |[alpha]|PA from three different constructs encoding |[alpha]|PA light chain (LC) and heavy chain cDNAs, including: (1) expression from a single CMV promoter with a poliovirus internal ribosome entry site (IRES) between the subunits [CMV(LC)IRES(HC)]; (2) expression of each subunit from its own CMV promoter [CMV(HC)CMV(LC)]; and (3) expression from one CMV promoter with a self cleaving peptide 2A between subunits [CMV(HC)2A(LC)]. These constructs were packaged into AAVrh10 vectors and evaluated for the expression of |[alpha]|PA in vitro following infection of 293 cells. At 72 hr post-infection, the |[alpha]|PA antibody titers (PA-specific ELISA) in the infected cell medium were 100 |[plusmn]| 3 for AAVrh10CMV(LC)IRES(HC), 60 |[plusmn]| 2 for AAVrh10CMV(HC)CMV(LC), and 600 |[plusmn]| 20 for A AVrh10CMV(HC)2A(LC), with the titer generated by AAVrh10CMV(HC)2A(LC) significantly higher than the other groups (p<0.001). All vectors were evaluated for the expression of |[alpha]|PA in vivo following intravenous administration of 1011 genome copies to male C57BL/6 mice. After 2 wk, serum titers of anti-PA (ELISA) were: AAVrh10CMV(LC)IRES(HC) 20 |[plusmn]| 2, AAVrh10CMV(HC)CMV(LC) 200 |[plusmn]| 40, and AAVrh10CMV(HC)2A(LC) 5300 |[plusmn]| 400 [AAVrh10CMV(HC)2A(LC) p<0.001 compared to other groups]. The AAVrh10CMV(HC)2A(LC) vector was administered (1011 genome copies) to male C57BL/6 mice via intrapleural or intravenous routes, and serum titers of |[alpha]|PA measured at various times. Mice administered the vector via the intrapleural route had serum |[alpha]|PA titers of 2400 |[plusmn]| 400, 6000 |[plusmn]| 1300, and 9700 |[plusmn]| 1200 at 1, 2, and 4 wk, respectively. Intravenous administration resulted in serum |[alpha]|PA titers of 2200 |[plusmn]| 100, 5400 |[plusmn]| 450, and 6700 |[plusmn]| 240 at 1, 2, and 4 wk, respectively. These data indicate that passive immunization with an AAVrh10CMV(HC)2A(LC) vector may be a convenient and highly effective approach for rapidly and persistently protecting susceptible populations against anthrax.

Postal Workers' Perspectives on Communication During the Anthrax Attack

In 2001, the nation experienced its first bioterrorism attack, in the form of anthrax sent through the U.S. Postal Service, and public health professionals were challenged to communicate with a critical audience, U.S. postal workers. Postal workers, the first cohort to receive public health messages during a bioterrorist crisis, offer a crucial viewpoint that can be used in the development of best practices in crisis and emergency risk communication. This article reports results of qualitative interviews and focus groups with 65 postal workers employed at three facilities: Trenton, New Jersey; New York City; and Washington, DC. The social context and changing messages were among the factors that damaged trust between postal workers and public health professionals. Lessons learned from this attack contribute to the growing body of knowledge available to guide communications experts and public health professionals charged with crisis and emergency risk communication with the public.

Figs--the earliest known ancient drug for cutaneous anthrax.

Anthrax is an often fatal bacterial infection, occurring in cutaneous, inhalational, gastrointestinal, and meningeal forms. Evaluation of anthrax treatment from ancient history may help healthcare providers to handle this serious disease more efficiently. To evaluate the biblical descriptions of anthrax, focusing on its therapy in ancient times. All biblical texts associated with anthrax were examined and passages relating to this disease were studied closely. Biblical passages such as: "Take a cluster of figs. And they took and laid it on the boil [anthrax], and he recovered," and "Let them take a cluster of figs, and lay it upon the boil [anthrax], and he shall recover," convincingly indicate that figs have healing properties in cutaneous anthrax lesions. On the basis of this study, the National Institutes of Health together with the pharmaceutical industry may consider to work on isolation of compounds from fig plants to develop products against cutaneous and possibly other forms of anthrax once screening tests are completed.

Nota Bene: Know Thine Enemy

T he anthrax bacillus is enjoying renewed notoriety as an agent of bioterrorism. Inhalation of about 10,000 Bacillus anthracis spores causes a systemic form of anthrax that is fatal unless treated immediately with antibiotics. This lethality is principally due to the tripartite toxin produced by the

Impaired neutrophil function in the cutaneous form of anthrax.

Spontaneous and Bacillus anthracis induced luminol-dependent chemiluminescence of neutrophils was studied in six patients with the cutaneous form of anthrax. Spontaneous chemiluminescence in anthrax was decreased compared to the healthy controls (p < 0.05). B. anthracis, opsonized by complement-containing sera from patients, induced chemiluminescence in neutrophils from control donors but not from patients. B. anthracis, opsonized by complement-free sera from the patients, did not cause an increase in chemiluminescence response in either the patient or the control neutrophils. Also, B. anthracis, opsonized with normal sera and nonopsonized, did not induce chemiluminescence in either patient or control neutrophils. It was concluded that oxidative metabolism by neutrophils is impaired in anthrax, whereas the functional capacity of antibodies seems to be unaffected.