Epidemiology of anthrax in wild animals and the control of anthrax epizootics in the Kruger National Park, South Africa.
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Animals↗
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[An outbreak of anthrax in Amur Province in 1954 (from experience in the diagnosis and control of anthrax)].
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Adolescent↗
[Isolation and study of an anthrax protective antigen. V. The dynamics of immunity in vaccination with a concentrated, purified sorbed chemical anthrax vaccine].
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Animals↗
BRAF status and mitogen-activated protein/extracellular signal-regulated kinase kinase 1/2 activity indicate sensitivity of melanoma cells to anthrax lethal toxin.
Anthrax lethal toxin, composed of protective antigen and lethal factor, was tested for cytotoxicity to human melanoma cell lines and normal human cells. Eleven of 18 melanoma cell lines were sensitive to anthrax lethal toxin (IC(50) < 400 pmol/L) and 10 of these 11 sensitive cell lines carried the V599E BRAF mutation. Most normal cell types (10 of 15) were not sensitive to anthrax lethal toxin and only 5 of 15 normal human cell types were sensitive to anthrax lethal toxin (IC(50) < 400 pmol/L). These cells included monocytes and a subset of endothelial cells. In both melanoma cell lines and normal cells, anthrax toxin receptor expression levels did not correlate with anthrax lethal toxin cytotoxicity. Furthermore, an anthrax toxin receptor-deficient cell line (PR230) did not show any enhanced sensitivity to anthrax lethal toxin when transfected with anthrax toxin receptor. Anthrax lethal toxin toxicity correlated with elevated phosphorylation levels of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) 1/2 in both melanoma cell lines and normal cells. Anthrax lethal toxin-sensitive melanoma cell lines and normal cells had higher phospho-MEK1/2 levels than anthrax lethal toxin-resistant melanoma cell lines and normal tissue types. U0126, a specific MEK1/2 inhibitor, was not toxic to anthrax lethal toxin-resistant melanoma cell lines but was toxic to 8 of 11 anthrax lethal toxin-sensitive cell lines. These results show that anthrax lethal toxin toxicity correlates with elevated levels of active MEK1/2 pathway but not with anthrax toxin receptor expression levels in both normal and malignant tissues. Anthrax lethal toxin may be a useful therapeutic for melanoma patients, especially those carrying the V599E BRAF mutation with constitutive activation of the mitogen-activated protein kinase pathway.
Antigens, Bacterial↗
Neutron-based sterilization of anthrax contamination.
With the anthrax threat becoming a reality, it is very important to have an effective way to sterilize areas contaminated by anthrax. Anthrax spores are the dormant form of the anthrax bacteria. They can germinate in tissues, producing new bacteria that release lethal toxins. Neutrons can be a powerful tool in our defense against anthrax contamination. Neutrons are elementary particles that have no charge, which allows them to be very penetrating, killing the anthrax spores on the surface and inside the containers. So neutrons have an advantage over other forms of radiation if deep penetration is required to kill biological organisms. A Cf neutron source allows for a low cost method of decontamination. It emits most neutrons in the 100 keV to 2 MeV energy regions, and a neutron in this energy region is 20 times more deadly than electrons or gamma rays in killing anthrax spores. If we just consider the first neutron collision with anthrax spores and that all the anthrax spores will not survive at the dose level above 2.0 x 10 Gy, our calculations show that a 0.5-g Cf neutron source within 20 min can generate 1.11 x 10 m fluence neutrons, which is good enough to kill the anthrax spores on the sample. An experimental confirmation of the above results may prove that to achieve 1.11 x 10 m fluence neutrons on the anthrax spore sample, the neutron irradiation time may be reduced dramatically or the Cf neutron source reduced to 0.1 g level or even less. The aim of this paper is to evaluate a feasible way to sterilize the anthrax contamination by using a Cf neutron source. Presently, we are mainly concentrating on the theoretical estimation of neutron fluence to see if the Cf neutron source can deliver enough neutron irradiation dose to kill the anthrax spores. Our future work will focus on experimental confirmation and Monte Carlo simulation by using Geant4 or MCNP codes. At that time, we will consider the effects of the real experimental setup, the shielding materials, the exact chemical components, and the biological structures of anthrax spores. We also need to consider the ways of carrying the anthrax spores, and this includes surface contamination, inside an envelope, or hidden in sealed metal containers and luggage.
Anthrax↗
Anthrax: a systematic review of atypical presentations.
During the 2001 US anthrax attacks, mortality from inhalational anthrax was significantly lower than had been reported historically, which was attributed in part to early identification and timely treatment. During future attacks, clinicians will rely on published descriptions of the clinical features of inhalational anthrax to rapidly diagnose patients and institute appropriate treatment. Published descriptions of typical inhalation anthrax usually include patients presenting with cough, dyspnea, or chest pain and found to have abnormal lung examination results with pleural effusions or enlarged mediastinum. The purpose of this article is to evaluate whether atypical presentations of inhalational anthrax occur and to describe the features of these presentations. We define atypical presentations as those in patients with confirmed anthrax infection who do not have known cutaneous, gastrointestinal, or inhalational ports of entry. We reviewed the case reports of 42 patients with atypical anthrax (published between 1900 and 2004) that may have had an inhalational source of infection to evaluate whether their clinical presentations differed from the typical findings of inhalational anthrax. Patients with atypical anthrax were less likely to have cough, chest pain, or abnormal lung examination results than patients with typical inhalational anthrax (P<.05 for all comparisons). A previously published screening protocol for patients with suspected anthrax correctly identified 91% of patients with atypical presentations. We conclude that although uncommon, atypical presentations of inhalational anthrax likely occur. Timely diagnosis and treatment of patients with inhalational anthrax require clinical awareness of the full spectrum of signs and symptoms associated with inhalational anthrax.
Algorithms↗
Anthrax revisited.
BACKGROUND: Anthrax is an ancient disease affecting animals and humans. Sporadic cases of anthrax and small epidemics have been seen from time to time in different parts of the world and in Africa. However many clinicians are not very familiar with the various presentations and management of anthrax. It is relevant for the health care workers to re-familiarise themselves with all aspects of anthrax, with the impending threat of bioterrorism. OBJECTIVE: To familiarise healthcare workers on all aspects of anthrax. STUDY SELECTION: To describe epidemiology pathogenesis, clinical features, management and prevention of anthrax including measures to take when weapons grade anthrax is suspected. DATA SYNTHESIS: Three forms of the disease are recognised, cutaneous, inhalational and intestinal. Cutaneous anthrax is the most common form. Inhalation anthrax is the most severe form of anthrax. The treatment of anthrax in most cases is penicillin, however with the threat of bioterrorism, intentional releases of anthrax spores in the environment has caused much concern. Weapons grade anthrax of more virulent strain and resistant to commonly used antibiotics is possible. CONCLUSION: In view of the different clinical presentations and outcomes it is important that health care workers re-familiarise themselves with the disease and in the event of bioterrorism are able to take appropriate measures.
Africa↗
Accuracy of screening for inhalational anthrax after a bioterrorist attack.
BACKGROUND: Bioterrorism using anthrax claimed five lives in the United States in 2001 and remains a potential public health threat. In the aftermath of a large-scale anthrax attack, mass screening to identify early inhalational anthrax may improve both the management of individual cases and the efficiency of health resource utilization. PURPOSE: To develop the evidence base for outpatient anthrax screening protocols by quantifying differences in clinical presentation between inhalational anthrax and common viral respiratory tract infections. DESIGN: Review, compilation, and data extraction from English-language case reports of inhalational anthrax and epidemiologic studies of influenza and other viral respiratory infections. DATA SOURCES: 13 reports of 28 cases of inhalational anthrax from 1920 to 2001 and 5 studies reporting on the clinical features of 2762 cases of influenza and 1932 cases of noninfluenza viral respiratory disease. DATA SYNTHESIS: Characterization of presenting clinical symptoms in anthrax and viral disease and calculation of likelihood ratios for the presence of selected clinical features. RESULTS: Fever and cough do not reliably discriminate between inhalational anthrax and viral respiratory tract infection. Features suggestive of anthrax include the presence of nonheadache neurologic symptoms (positive likelihood ratio cannot be calculated), dyspnea (positive likelihood ratio, 5.3 [95% CI, 3.7 to 7.4]), nausea or vomiting (positive likelihood ratio, 5.1 [CI, 3.0 to 8.5]), and finding of any abnormality on lung auscultation (positive likelihood ratio, 8.1 [CI, 5.3 to 12.5]). In contrast, rhinorrhea (positive likelihood ratio, 0.2 [CI, 0.1 to 0.4]) and sore throat (positive likelihood ratio, 0.2 [CI, 0.1 to 0.5]) are more suggestive of viral respiratory tract infection. CONCLUSION: Inhalational anthrax has characteristic clinical features that are distinct from those seen in common viral respiratory tract infections. Screening protocols based on these features may improve rapid identification of patients with presumptive inhalational anthrax in the setting of a large-scale anthrax attack.
Anthrax↗
Anthrax lethal toxin blocks MAPK kinase-dependent IL-2 production in CD4+ T cells.
Anthrax lethal toxin (LT) is a critical virulence factor that cleaves and inactivates MAPK kinases (MAPKKs) in host cells and has been proposed as a therapeutic target in the treatment of human anthrax infections. Despite the potential use of anti-toxin agents in humans, the standard activity assays for anthrax LT are currently based on cytotoxic actions of anthrax LT that are cell-, strain-, and species-specific, which have not been demonstrated to occur in human cells. We now report that T cell proliferation and IL-2 production inversely correlate with anthrax LT levels in human cell assays. The model CD4+ T cell tumor line, Jurkat, is a susceptible target for the specific protease action of anthrax LT. Anthrax LT cleaves and inactivates MAPKKs in Jurkat cells, whereas not affecting proximal or parallel TCR signal transduction pathways. Moreover, anthrax LT specifically inhibits PMA/ionomycin- and anti-CD3-induced IL-2 production in Jurkat cells. An inhibitor of the protease activity of anthrax LT completely restores IL-2 production by anthrax LT-treated Jurkat cells. Anthrax LT acts on primary CD4+ T cells as well, cleaving MAPKKs and leading to a 95% reduction in anti-CD3-induced proliferation and IL-2 production. These findings not only will be useful in the development of new human cell-based bioassays for the activity of anthrax LT, but they also suggest new mechanisms that facilitate immune evasion by Bacillus anthracis. Specifically, anthrax LT inhibits IL-2 production and proliferative responses in CD4+ T cells, thereby blocking functions that are pivotal in the regulation of immune responses.
Antigens, Bacterial↗
Gastrointestinal adverse reactions following anthrax vaccination: an analysis of the Vaccine Adverse Events Reporting System (VAERS) database.
BACKGROUND/AIMS: The Institute of Medicine (IOM) of the United States Academy of Sciences in 2000 encouraged the evaluation of active long-term monitoring studies of large populations to further evaluate the relative safety of anthrax vaccine. Anthrax is a deadly bacterial infectious disease that currently has been engineered as a biological warfare agent. The vaccine produced against anthrax is a cell-free crude culture of the various toxin components of the natural disease. The U.S. military current goal is to vaccinate its entire personnel by 2003. The purpose of this study was to evaluate anthrax vaccination and its association with arthritic, immunological and gastrointestinal adverse reactions based upon analysis of the Vaccine Adverse Events Reporting System (VAERS) database. METHODOLOGY: We analyzed the VAERS database from 15 December 1997 to 12 April 2000. We also compared the incidence of anthrax adverse reactions with the incidence of adverse reactions reported to VAERS after adult tetanus vaccination. RESULTS: Anthrax vaccine was one of the most reactogenic vaccines included in VAERS. The incidence of adverse reactions reported following anthrax vaccine was higher for every reaction analyzed in comparison to the adult vaccine control groups. CONCLUSIONS: The current anthrax vaccine may be acceptable in military populations in impending threat of anthrax exposure, the cost-benefits of vaccination in less high risk military populations may be more questionable. Civilian anthrax vaccination will require a less reactogenic vaccine. Civilian doctors should be aware of anthrax vaccine adverse reactions. Military and civilian doctors should also be diligent in their reporting to VAERS of cases of adverse reactions to anthrax vaccine.
Adult↗
Human behavioural factors implicated in outbreaks of human anthrax in the Tamale municipality of northern Ghana.
The knowledge, attitude, beliefs and practices of cattle owners, herdsmen, butchers and meat consumers about anthrax were used to provide a better understanding of the major factors responsible for the frequent outbreaks of human anthrax in the Tamale municipality of northern Ghana. A total of 96% of the respondents, made up of 50 cattle owners, 50 herdsmen, 25 butchers and 125 consumers, knew of anthrax and the clinical signs indicative of anthrax in cattle. However, very few knew the causative agent and many attributed the disease to the supernatural. Eight percent of the respondents believed that herbal preparations could protect against human anthrax, while 9% indicated that they would seek help from traditional practitioners or herbalists, if they suspected anthrax. A significant proportion of respondents were of the view that animals, which had died of unknown causes could be eaten because they served as a source of inexpensive meat for the community, especially if the meat was cooked with herbs which was commonly thought to prevent anthrax. These attitudes, taken together with the low income of the population studied, made the consumption of meat from animals, which had died of unknown causes, an attractive option. This increased the vulnerability to human anthrax in an area with frequent anthrax outbreaks in livestock. The results of this study suggest that a public education campaign involving both veterinary and local health personnel on the actual cause and prevention of anthrax could reduce outbreaks of anthrax in people.
Animals↗
[Anthrax--the past, present and future].
HISTORY: Anthrax has been known since ancient times. Besides some references in the Old Testament, there is evidence of plagues in ancient Egypt, as well as descriptions of the disease by the Roman poet Virgil. ETIOLOGY: Anthrax is caused by Bacillus anthracis, unmovable, aerobic, gram-positive rods. It forms spores, which can survive for years in the environment. PATHOGENESIS: Capsular polypeptide and anthrax toxin are the principal virulence factors of Bacillus anthracis. Anthrax toxin consists of three proteins called protective antigen, edema factor, and lethal factor. It is thought that the inflammatory mediator--lethal factor is stored within the macrophage during the early stage of infection. It is rapidly released in large amounts into the blood stream and once the threshold for lysis is reached, it may be the cause of sudden death. EPIDEMIOLOGY: Grass-eating animals are usually infected by the bacilli from grass and ground. The disease is transmitted to people by contact with the sick animals or their products, such as wool, skin, meat etc. CLINICAL FEATURES: Two clinical forms exist: outer--cutaneous and inner, including inhalation and gastrointestinal anthrax. While cutaneous anthrax is easily cured, the inner forms have high mortality rates. DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS: The diagnosis is easily established in cutaneous cases, characterized by black eschar. Severe intoxication and collapse during the course of bronchopneumonia or hemorrhagic enteritis should arise suspicion of anthrax. THERAPY: Hospitalization of patients is mandatory. Bacillus anthracis is susceptible to a number of antibiotics, including penicillin, erythromycin, tetracyclines, cephalosporins etc. PREVENTION: General veterinary prevention including vaccination of livestock and control of products is very important. The vaccine consists of anthrax bacillus that is attenuated. The endangered population, such as animal workers and military personnel should be vaccinated. Annual schedule of booster immunization must be maintained. ANTHRAX AS A BIOLOGICAL WEAPON: Anthrax has been developed as a weapon of mass destruction since World War I. During accidental release from a biological warfare factory in the former Soviet Union, 68 people died. The ease of laboratory production and its dissemination via aerosol led to its adoption by terrorists, as shown by recent happenings in the USA. CONCLUSION: A good knowledge of anthrax, its transmission and potentials as a biological weapon is essential for timely prevention and protection.
Anthrax↗
Anthrax.
Anthrax is caused by Bacillus anthracis, an encapulated and spore-forming bacillus. The disease is usually contracted through uptake of spores that remain viable in the contaminated soil for many years. Anthrax is primarily a disease of herbivorous animals and is uncommon in humans who may get the infection through contact with contaminated animals or their products. Anthrax spores germinate after entering the body through skin abrasions (cutaneous anthrax) or by inhalation (inhalation anthrax) or ingestion (gastrointestinal anthrax) and multiply to produce two exotoxins which determine the virulence along with capsule. Although most cases occur within 48 hours of exposure, germination of spores may occur upto 60 days later. While inhalation anthrax is almost always fatal, intestinal anthrax results in death in 25% to 60% of cases. Upto 20% of cases having cutaneous anthrax may die. Antibiotics are effective if the disease is recognised early and treated appropriately. Penicillin is the drug of choice when disease occurs in natural setting. Ciprofloxacin is recommended when aerosols of anthrax spores are used as bioweapon, prophylactic antibiotics should not be prescribed until risk of exposure is considered real by experts.
Animals↗
Cutaneous anthrax in adults: a review of 25 cases in the eastern Anatolian region of Turkey.
BACKGROUND: The clinical features, therapy and outcome of anthrax cases from the Elazig province (the eastern Anatolian region) of Turkey seen in our clinic over an 8-year period were reviewed. PATIENTS AND METHODS: The records of 25 anthrax cases observed in our clinic during the period January 1994 to April 2002 were examined. RESULTS: All cases were cutaneous; 18 (72%) patients exhibited malignant pustules and seven (28%) malignant edema. Three of the patients with a malignant pustule developed anthrax sepsis when admitted to our clinic. All cases were treated with penicillin. One patient who had penicillin allergy was treated with ciprofloxacin. In addition, patients with malignant edema were also treated with systemic corticosteroids (methylprednisolone or dexamethasone). Two patients died due to anthrax sepsis; one case with anthrax sepsis recovered. The mortality rate was 8%. DISCUSSION: Anthrax is still a reality in Turkey. Cutaneous anthrax should be considered in any patient with a painless ulcer with vesicles, edema and a history of exposure to animals or animal products. In our series, penicillin and ciprofloxacin were effective in treatment of anthrax. Our anthrax sepsis case demonstrates that anthrax sepsis is not always fatal if antibiotic treatment is given early after diagnosis.
Adolescent↗
A national register of historic and contemporary anthrax foci.
Anthrax in Russia has for a long time posed a serious problem for public health and veterinary services. At the beginning of the century, 40-60 thousand cases of this infection were annually reported in the country in agricultural animals and about 10-20 thousand cases in people where each fourth (25%) was dying. In the Russian Federation the registration of anthrax foci is obligatory for veterinary as well as for sanitary-epidemiological services. So our initial project, funded by the International Technical and Scientific Center in Moscow, has envisaged the collection of all data of known anthrax foci, including the village name, agricultural council, region, oblast and year of occurrence. The objective is to assemble a reference handbook, "Register of stable anthrax sites in the Russian Federation", containing organized information on more than 10 000 anthrax foci occurring during the past 100 years. Such a study makes it possible to identify regions characterized by the highest concentrations of stationary anthrax sites in Russia, to identify trends in expressed activity of such sites through the periodic emergence of disease in humans and animals, and to determine the factors contributing to the formation of such trends. In doing this, it makes it possible to develop contingency plans for different risk locations (i.e. high risk of persistent infection, high risk of sporadic occurrence, low risk areas, etc.) in terms of anthrax in Russia, to identify high risk areas and develop a differentiated strategy of vaccination and other control strategies, and to develop preventive recommendations to reduce risk in high risk areas. It is now important to develop the second step of the project: to develop in depth studies of particular clusters to determine which factors are associated with Russian anthrax outbreaks. Maps will greatly enhance the value of this work in terms of spatial analysis. Furthermore, this supplementary project will allow the incorporation of powerful Geographic Information System (GIS) electronic mapping technology so that natural geographic features, such as soil type, climate, etc., can be compared with anthrax distributions in Russia using standard GIS and statistical analysis. At the present time, it is imperative to develop a detailed understanding of the world's distribution of anthrax and what geographic factors determine its prevalence.
Anthrax↗
Anthrax explodes in an Australian summer.
Anthrax occurred on 83 properties in an area of north central Victoria between 26 January and 26 March in the summer of 1997. Anthrax had not been recorded in the outbreak area since records were initiated in 1914, although anthrax did occur in the general area in the 1880s to 1890s. Standard Australian control measures were applied to the properties, including quarantine, tracing movements of animals on and off affected properties, secure disposal of carcases by burning, enhanced surveillance of stock generally in the area and the use of local disaster control procedures including an alert of health authorities. As affected property numbers began to increase dramatically from 8 February, it was decided to use blanket area vaccination to control the disease. By 26 February, the epidemic curve had returned to the base line and a buffer vaccination zone of 457 farms holding 78,649 cattle was formed by early March 1997. Between 26 January and 26 March when the outbreak was declared over, 202 cattle and 4 sheep were confirmed to have died of anthrax. Between 27 March and early November a further 26 cattle were confirmed as dying due to anthrax and 14 of these had not had previous vaccination, including four young calves and one horse. One new property within the vaccination buffer zone had an anthrax case in a cow in early November 1997. By mid-November 1997, all previously infected and all neighbouring properties within 1 km were compulsorily re-vaccinated, as were all calves when two months of age and all introduced cattle. In 1998, only two confirmed cases of anthrax were diagnosed; both were vaccinated calves on farms which had had multiple cases during the outbreak. The public reaction and attention fueled by unprecedented media attention led to intense international scrutiny from countries where anthrax is a particular zoonotic problem. Very strong representations had to be made about the safety of livestock and livestock products that came from Victoria. This event has demonstrated that there is a need to review OIE and other requirements and recommendations covering anthrax where strict restrictions are placed on livestock and livestock products to protect livestock and human populations against anthrax infection.
Animals↗
Anthrax--an overview.
Anthrax, a disease of mammals (including humans), is caused by a spore-forming Gram-positive bacilli called Bacillus anthracis. Anthrax is one of the oldest threats to humanity, and remains endemic in animals in many parts of the world. The incidence of anthrax has decreased in developed countries, but it remains a considerable health problem in developing countries. The disease is transmitted to humans by contact with sick animals or their products, such as wool, skin, meat etc. Capsular polypeptide and anthrax toxin are the principal virulence factors of B. anthracis. Anthrax toxin consists of three proteins called protective antigen, edema factor, and lethal factor, each of which is nontoxic but acts synergistically. Human anthrax has three major clinical forms: cutaneous, inhalational, and gastrointestinal. The diagnosis is easily established in cutaneous cases, characterized by black eschar. Severe intoxication and collapse during the course of bronchopneumonia or hemorrhagic enteritis should prompt suspicion of anthrax. Treatment with antibiotics is mandatory. If untreated, anthrax in all forms can lead to septicemia and death. Recently, considerable attention has been focused on the potential for B. anthracis to be used in acts of biological terrorism. The ease of laboratory production and its dissemination via aerosol led to its adoption by terrorists, as shown by recent events in the USA. A good knowledge of anthrax, its epidemiology, pathogenesis, clinical forms and potential as a biological weapon is essential for timely prevention and treatment. This review summarizes the current knowledge on anthrax.
Animals↗
Prophylaxis and therapy of inhalational anthrax by a novel monoclonal antibody to protective antigen that mimics vaccine-induced immunity.
The neutralizing antibody response to the protective antigen (PA) component of anthrax toxin elicited by approved anthrax vaccines is an accepted correlate for vaccine-mediated protection against anthrax. We reasoned that a human anti-PA monoclonal antibody (MAb) selected on the basis of superior toxin neutralization activity might provide potent protection against anthrax. The fully human MAb (also referred to as MDX-1303 or Valortim) was chosen from a large panel of anti-PA human MAbs generated using transgenic mice immunized with recombinant PA solely on the basis of in vitro anthrax toxin neutralization. This MAb was effective in prophylactic and postsymptomatic treatment of rabbits exposed to aerosolized anthrax spores, and a single intramuscular injection of 1 mg/kg of body weight fully protected cynomolgus monkeys challenged with aerosolized anthrax spores. Importantly, MAb 1303 defines a novel neutralizing epitope that requires Fc receptor engagement for maximal activity. F(ab')2 fragments of MAb 1303, which retain equivalent affinity for PA, are 10- to 100-fold less potent in neutralizing anthrax toxin in vitro. Addition of Fc receptor-blocking antibodies also greatly reduced the activity of MAb 1303. Moreover, we found that the neutralizing activity of mouse, rabbit, and human antisera elicited by PA vaccines was effectively abrogated by blocking Fc receptors. Selection of an anti-PA MAb by using a functional assay that is a surrogate for protection has resulted in the identification of a fully human MAb with potent activity in vivo and uncovered a previously unrecognized mechanism of antibody-mediated toxin neutralization that is important for currently used anthrax vaccines.
Animals↗