Review Article

Medical Progress

Anthrax

Terry C. Dixon, B.S., Matthew Meselson, Ph.D., Jeanne Guillemin, Ph.D., and Philip C. Hanna, Ph.D.

N Engl J Med 1999; 341:815-826September 9, 1999

Article

Anthrax is an often fatal bacterial infection that occurs when Bacillus anthracis endospores enter the body through abrasions in the skin or by inhalation or ingestion.1 It is a zoonosis to which most mammals, especially grazing herbivores, are considered susceptible. Human infections result from contact with contaminated animals or animal products, and there are no known cases of human-to-human transmission. Human anthrax is not common, and only one of us has seen a case. Cutaneous anthrax, the most common form, is usually curable. A small percentage of cutaneous infections become systemic, and these can be fatal. Systemic infection resulting from inhalation of the organism has a mortality rate approaching 100 percent, with death usually occurring within a few days after the onset of symptoms.2 The rate of mortality among persons with infection resulting from ingestion is variable, depending on the outbreak, but it may also approach 100 percent. Whatever the portal of entry, systemic anthrax involves massive bacteremia and toxemia with nondescript initial symptoms until the onset of hypotension, shock, and sudden death. Manifestations of advanced disease, including shock and sudden death, are believed to result from the action of the exotoxin complex secreted by anthrax bacilli.1,3 The efficacy of therapy, if initiated during the incubation period, and the rapid course of the disease once symptoms appear make early intervention an absolute necessity. Inglesby et al. have provided a description of the policies and strategies for dealing with anthrax as a biologic weapon.4 The goal of this article is to familiarize physicians with the current understanding of the pathogenesis, diagnosis, prevention, and treatment of anthrax.

Pathogenesis

Anthrax infections are initiated by endospores of B. anthracis, a gram-positive soil organism. Anthrax endospores do not divide, have no measurable metabolism, and are resistant to drying, heat, ultraviolet light, gamma radiation, and many disinfectants.5 In some types of soil, anthrax spores can remain dormant for decades. Their hardiness and dormancy have allowed anthrax spores to be developed as biologic weapons by a number of nations, although their only known use in war was by the Japanese army in Manchuria in the 1940s.6 All known anthrax virulence genes are expressed by the vegetative form of B. anthracis that results from the germination of spores within the body.

The course of infection and clinical manifestations are depicted in Figure 1Figure 1Pathophysiology of Anthrax.. Endospores introduced into the body by abrasion, inhalation, or ingestion are phagocytosed by macrophages and carried to regional lymph nodes. Endospores germinate inside the macrophages and become vegetative bacteria7,8; the vegetative bacteria are then released from the macrophages, multiply in the lymphatic system, and enter the bloodstream, until there are as many as 10⁷ to 10⁸ organisms per milliliter of blood, causing massive septicemia. Once they have been released from the macrophages, there is no evidence that an immune response is initiated against vegetative bacilli. Anthrax bacilli express virulence factors, including toxin and capsule.1 The resulting toxemia has systemic effects that lead to the death of the host.

The major virulence factors of B. anthracis are encoded on two virulence plasmids, pXO1 and pXO2. The toxin-bearing plasmid, pXO1, is 184.5 kilobase pairs (kbp) in size and codes for the genes that make up the secreted exotoxins. The toxin-gene complex is composed of protective antigen, lethal factor, and edema factor.9 The three exotoxin components combine to form two binary toxins. Edema toxin consists of edema factor, which is a calmodulin-dependent adenylate cyclase,10,11 and protective antigen, the binding moiety that permits entry of the toxin into the host cell. Increased cellular levels of cyclic AMP upset water homeostasis and are believed to be responsible for the massive edema seen in cutaneous anthrax. Edema toxin inhibits neutrophil function in vitro,12 and neutrophil function is impaired in patients with cutaneous anthrax infection.13 Lethal toxin consists of lethal factor, which is a zinc metalloprotease14-16 that inactivates mitogen-activated protein kinase kinase in vitro,17,18 and protective antigen, which acts as the binding domain. Lethal toxin stimulates the macrophages to release tumor necrosis factor α and interleukin-1β, which are partly responsible for sudden death in systemic anthrax (Figure 1, inset).3,15,19

The smaller capsule-bearing plasmid, pXO2, is 95.3 kbp in size and codes for three genes (capB, capC, and capA) involved in the synthesis of the polyglutamyl capsule.20 The exotoxins are thought to inhibit the immune response mounted against infection, whereas the capsule inhibits phagocytosis of vegetative anthrax bacilli. The expression of all known major virulence factors is regulated by host-specific factors such as elevated temperature (≥37°C) and carbon dioxide concentration (≥5 percent), and by the presence of serum components.21,22 Regulation of the expression of the toxin and capsule genes is mediated by the transcriptional activator AtxA, whose activity appears to be affected by the previously mentioned environmental conditions.23-25 Expression of the capsule gene is also controlled by its own transcriptional regulator, AcpA.26 Both plasmids are required for full virulence; the loss of either one results in an attenuated strain. Historically, bacterial strains for anthrax vaccine were made by rendering virulent strains free of one or both plasmids. Pasteur, an avirulent pXO2-carrying strain, is encapsulated but does not express exotoxin components.1 Sterne, an attenuated strain that carries pXO1, can synthesize exotoxin components but does not have a capsule.1

Clinical Manifestations

Cutaneous Anthrax

Cutaneous anthrax accounts for 95 percent of all anthrax infections in the United States.27-30 The name anthrax (from the Greek for coal) refers to the typical black eschar that is seen on affected areas (Figure 2Figure 2Cutaneous Anthrax Infection of the Hand and Cheek.). Patients often have a history of occupational contact with animals or animal products. The most common areas of exposure are the head, neck, and extremities, although any area can be involved. Pathogenic endospores are introduced subcutaneously through a cut or abrasion. There are a few case reports of transmission by insect bites, presumably after the insect fed on an infected carcass.31,32 The primary skin lesion is usually a nondescript, painless, pruritic papule that appears three to five days after the introduction of endospores. In 24 to 36 hours, the lesion forms a vesicle that undergoes central necrosis and drying, leaving a characteristic black eschar surrounded by edema and a number of purplish vesicles. The edema is usually more extensive on the head or neck than on the trunk or extremities.33 The common description “malignant pustule” is actually a misnomer, because the cutaneous lesion is not purulent and is characteristically painless. A painful, pustular eschar in a febrile patient indicates a secondary infection, most often with staphylococcus or streptococcus.34

Although cutaneous anthrax can be self-limiting, antibiotic treatment is recommended. Lesions resolve without complications or scarring in 80 to 90 percent of cases. Malignant edema is a rare complication characterized by severe edema, induration, multiple bullae, and symptoms of shock.35,36 Malignant edema involving the neck and thoracic region often leads to breathing difficulties that require corticosteroid therapy or intubation. A few cases have been reported of temporal arteritis associated with cutaneous anthrax infection and of corneal scarring from palpebral cutaneous anthrax.37,38 Histologic examination of anthrax skin lesions shows necrosis and massive edema with lymphocytic infiltrates. There is no liquefaction or abscess formation, indicating that the lesions are not suppurative. Focal points of hemorrhage are evident, with some thrombosis.39 Gram's staining reveals bacilli in the subcutaneous tissue.39

Gastrointestinal and Oropharyngeal Anthrax

Gastrointestinal anthrax, which can be fatal, has not been reported in the United States. The symptoms appear two to five days after the ingestion of endospore-contaminated meat from diseased animals.40 Therefore, multiple cases can occur within individual households.40,41 An unusually prolonged outbreak was attributed to the consumption of stored meat products.42 It is presumed that bacterial inoculation takes place at a breach in the mucosal lining, but exactly where the endospores germinate is unknown. On pathological examination, bacilli can be seen microscopically in the mucosal and submucosal lymphatic tissue, and there is gross evidence of mesenteric lymphadenitis.43 Ulceration is always seen. It is not known whether ulceration occurs only at sites of bacterial infection or is distributed more diffusely as a result of the action of anthrax toxin.43-45 Microscopical examination of affected tissues reveals massive edema and mucosal necrosis at infected sites.45 Inflammatory infiltrates are seen that are similar to those in cutaneous anthrax. Gram's staining of peritoneal fluid may reveal numerous large gram-positive bacilli.40,46

Although mediastinal widening is considered pathognomonic of inhalational anthrax, it has also been reported in a case of gastrointestinal anthrax.47 Associated symptoms include fever and diffuse abdominal pain with rebound tenderness. There are reports of both constipation and diarrhea; the stools are either melenic or blood-tinged.46,48 Because of ulceration of the gastrointestinal mucosa, patients often vomit material that is blood-tinged or has a coffee-ground appearance. Ascites develops with concomitant reduction in abdominal pain two to four days after the onset of symptoms. The appearance of the ascites fluid ranges from clear to purulent, and it often yields colonies of B. anthracis when cultured. Morbidity is due to blood loss, fluid and electrolyte imbalances, and subsequent shock. Death results from intestinal perforation or anthrax toxemia. If the patient survives, most of the symptoms subside in 10 to 14 days.48

Oropharyngeal anthrax is less common than the gastrointestinal form. It is also associated with the ingestion of contaminated meat. Initial symptoms include cervical edema and local lymphadenopathy, which cause dysphagia and respiratory difficulties. Lesions can be seen in the oropharynx and usually have the appearance of pseudomembranous ulcerations. This form is milder than the classic gastrointestinal disease and has a more favorable prognosis.34,48

Inhalational Anthrax

Inhalational anthrax is rare, usually occurring after the inhalation of pathogenic endospores from contaminated animal hides or products. Before the introduction of hygienic measures in the 1960s, including vaccination, workers in goat-hair mills, for example, were regularly exposed to high concentrations of viable anthrax spores. Nevertheless, for reasons that are not understood, few cases of inhalational anthrax occurred among them.49-51 When dispersed in the atmosphere as an aerosol, anthrax spores can present a respiratory hazard even far downwind from the point of release, as demonstrated by animal tests on Gruinard Island in the United Kingdom,52-55 and by an accidental release from a military biologic facility in the city of Sverdlovsk in the former Soviet Union.2,56-58

Inhalational anthrax is usually fatal, even with aggressive antimicrobial therapy. It appears that only about one fifth of those who contracted inhalational anthrax in Sverdlovsk recovered.2 Anthrax spores are about 1 to 2 μm in diameter, a size that is optimal for inhalation and deposition in the alveolar spaces.51,59-61 Although the lung is the initial site of contact, inhalational anthrax is not considered a true pneumonia. In most but not all cases, there is no infection in the lungs.58,62 Rather, the endospores are engulfed by alveolar macrophages and transported by them to the mediastinal and peribronchial lymph nodes, with the spores germinating en route. Anthrax bacilli multiply in the lymph nodes, causing hemorrhagic mediastinitis, and spread throughout the body in the blood.43,62

Data from the Sverdlovsk outbreak indicate a modal incubation time of approximately 10 days for inhalational anthrax. However, the onset of symptoms occurred up to six weeks after the reported date of exposure.2,57 Such long incubation times presumably reflect the ability of viable anthrax spores to remain in the lungs for many days.51,63,64 Longer incubation periods may be associated with smaller inocula.

The initial symptoms most often reported are fever, nonproductive cough, myalgia, and malaise, resembling those of a viral upper respiratory tract infection. Early in the course of the disease, chest radiographs show a widened mediastinum, which is evidence of hemorrhagic mediastinitis, and marked pleural effusions. After one to three days, the disease takes a fulminant course with dyspnea, strident cough, and chills, culminating in death.34,59 In Sverdlovsk, the mean time between the onset of symptoms and death was 3 days (range, 1 to 10). Although accompanying evidence of clinical signs of pneumonia in these cases is lacking, some of the autopsies from the Sverdlovsk outbreak showed a focus of necrotizing hemorrhagic pneumonitis, possibly at the portal of infection.58 Submucosal hemorrhages occurred in the trachea and bronchi, with hemorrhage and necrosis of peribronchial lymph nodes. Hemorrhagic mediastinal lymph nodes represent the primary lesion; however, gastrointestinal and leptomeningeal lesions are the result of hematogenous spread.

There may be wide individual variation in susceptibility to inhalational anthrax, as suggested by experimental studies in nonhuman primates and by the absence of persons younger than 24 years among the 66 deaths reported in the Sverdlovsk outbreak.2,51,57

Anthrax Meningitis

Involvement of the meninges by B. anthracis is a rare complication of anthrax.65 The most common portal of entry is the skin, from which the organisms can spread to the central nervous system by hematogenous or lymphatic routes. Anthrax meningitis also occurs in cases of pulmonary and gastrointestinal anthrax.58,66 Anthrax meningitis is almost always fatal, with death occurring one to six days after the onset of illness, despite intensive antibiotic therapy. In the few cases in which patients have survived, antibiotic therapy was combined with the administration of antitoxin, prednisone, or both.65,67 In addition to common meningeal symptoms and nuchal rigidity, the patient has fever, fatigue, myalgia, headache, nausea, vomiting, and sometimes agitation, seizures, and delirium. The initial signs are followed by rapid neurologic degeneration and death. The pathological findings are consistent with a hemorrhagic meningitis, with extensive edema, inflammatory infiltrates, and numerous gram-positive bacilli in the leptomeninges.43,68 The cerebrospinal fluid is often bloody and contains many gram-positive bacilli.69 Gross examination at autopsy finds extensive hemorrhage of the leptomeninges, which gives them a dark red appearance described as “cardinal's cap.”58

Diagnosis

Differential Diagnosis

Table 1Table 1Differential Diagnosis of Clinical Manifestations of Anthrax. summarizes the differential diagnosis of anthrax. In cutaneous anthrax, the painless, blackened, necrotic eschar is limited to the late stages of the infection. The ulcerative eschar of cutaneous anthrax must be differentiated from other papular lesions that present with regional lymphadenopathy. If the lesion is purulent and the regional lymph nodes are palpable, staphylococcal lymphadenitis is the most likely cause, although cutaneous anthrax lesions can be superinfected with pyogenic bacteria.70

The initial symptoms of inhalational anthrax are nondescript or “flulike” and are similar to those of atypical pneumonia from other causes. The prognosis is improved if early treatment is implemented, so that a high level of suspicion is necessary if there is a chance of exposure to anthrax. The cardiopulmonary collapse associated with a history of radiographic evidence of mediastinal widening in the late stages of inhalational anthrax must be differentiated from cardiovascular collapse with noninfectious causes, such as dissecting or ruptured aortic aneurysm and the superior vena cava syndrome. Anthrax infection is unusual in that mediastinal changes can be detected early in the course of infection by chest radiography, although similar pictures can be seen in acute bacterial mediastinitis and fibrous mediastinitis due to Histoplasma capsulatum.71 Less specific findings include pleural effusions and radiographic evidence of pulmonary edema. Silicosis, siderosis, alveolar proteinosis, and sarcoidosis are often alternative causes of chronic mediastinitis in patients with the relevant occupational history and previous chest radiographs demonstrating long-standing mediastinal widening.

When ingestion of contaminated meat is suspected, the symptoms of an acute abdomen should be considered as possible early signs of intestinal anthrax infection. Hemorrhagic meningitis caused by anthrax must be distinguished from subarachnoid hemorrhage by computed tomography without contrast. To distinguish hemorrhagic meningitis caused by B. anthracis from that caused by other bacteria, Gram's staining and culture of cerebrospinal fluid should be performed.68 In addition to the above indictors, the clinician should consider anthrax if there is a history of contact with materials that may be contaminated with spores, such as infected farm animals and imported hides, or of travel to places where anthrax is endemic. Because of the remote possibility of an anthrax aerosol attack, clinicians should be alert to any sudden deaths of previously healthy persons from undiagnosed disease and report them promptly to the Centers for Disease Control and Prevention and other appropriate public health officials.

Bacteriologic Tests

B. anthracis is a nonmotile, gram-positive, aerobic rod 1.2 to 10 μm in length and 0.5 to 2.5 μm in width that is capable of forming central or terminal spores (Figure 3Figure 3Photomicrographs of Bacillus anthracis Vegetative Cells and Spores.).72 It is part of the B. cereus group of bacilli, which consists of B. cereus, B. anthracis, B. thurin-giensis, and B. mycoides.73 The bacteria in this group tend to be dismissed by clinical microbiology laboratories as contaminants unless the physician specifically requests testing.73 Except for B. anthracis, all members of this group are resistant to penicillin because they produce chromosomally encoded beta-lactamases.74 B. anthracis is easy to differentiate from other members of the B. cereus group by observing the morphologic features of the colony on a blood-agar plate. Colonies of most B. anthracis isolates are nonhemolytic and are white to gray, often looking like ground glass.75 The unusually tenacious colonies are able to retain their shape when manipulated. When inoculated onto nutrient agar containing 0.7 percent bicarbonate and grown overnight at 37°C in the presence of 5 to 20 percent carbon dioxide, B. anthracis will form its characteristic poly-d-glutamic acid capsule.76 These colonies have a mucoid appearance, and the capsule can be demonstrated microscopically in a colony smear stained with McFadyean's polychrome methylene blue or India ink.75 Blood samples obtained from patients late in the course of infection and stained in the same manner will reveal large numbers of encapsulated bacilli. Bacilli can also be observed in and cultured from ascites fluid, pleural effusions, cerebrospinal fluid (in cases of meningitis),77 and fluid carefully expressed from the eschar, although expressing eschar fluid is not recommended because it can cause dissemination of the pathogen.78

Patients with systemic disease often die before positive blood cultures can be obtained, making early diagnosis and treatment crucial. If the samples are likely to be contaminated with other bacillus species, polymyxin–lysozyme–EDTA–thallous acetate agar is used as a selective medium for B. anthracis.79 The API 50 CH test strip (API Laboratory Products, Plainview, N.Y.) can be used in conjunction with the API 20E test strip to identify a number of bacillus species, including B. anthracis.80 Blood cultures in cases of systemic anthrax infection are almost always positive, because of the large numbers of bacterial cells in the circulation.1 Cultures of tissue from skin lesions, however, are not useful diagnostically, because the rate of positive cultures does not exceed 60 to 65 percent, probably owing to the use of antimicrobial therapy or the microbicidal activity of local antagonistic skin flora.81 There are reports of clinical isolates of B. anthracis that are resistant to penicillin.31,82 Because of the potential for drug-resistant strains, including deliberately modified strains, antibiotic-susceptibility testing should be performed on all isolates.

Serologic and Immunologic Tests

The major immunogenic proteins of B. anthracis appear to be capsular antigens and the exotoxin components. Specific enzyme-linked immunosorbent assays (ELISAs) that show a quadrupling of the titer of antibodies against these components are diagnostic of past infection or vaccination. The most reliable indicators are the titers of antibody to protective antigen and to capsular components.73,83,84 In studies of the measurement of antibody titers by ELISA, the sensitivity of possible indicators was as follows: 72 percent for protective antigen, 95 to 100 percent for capsule antigens, 42 percent for lethal factor, and 26 percent for edema factor.85 Enzyme-linked immunoelectrotransfer blotting provided a higher specificity when used in conjunction with ELISA-based testing.85 Indirect microhemagglutination gives results similar to those obtained with ELISA but has certain drawbacks, including the short shelf life of antigen-sensitized red-cell preparations, the limited reproducibility of the test, and longer preparation times.86

Immunologic detection of the exotoxins in blood during systemic infection is possible with similar tests if antibodies to anthrax toxins are available, but those tests are unreliable for diagnosis. Thus, although these tests are of epidemiologic value, they have little diagnostic value in acute illness.83 During systemic infections, antibodies to toxin or capsular components cannot be detected until late in the course of the disease, often when it is too late to initiate treatment.73 In treated infections, no increase in the antitoxin antibody titer is seen. The anthraxin skin test, consisting of subdermal injection of a commercially produced chemical extract of an attenuated strain of B. anthracis, is available for the diagnosis of acute and previous cases of anthrax.81,87,88 In one study the skin test diagnosed 82 percent of cases one to three days after the onset of symptoms and 99 percent of cases by the end of the fourth week.81 The skin test may be suitable for both rapid diagnosis of acute cases and the retrospective analysis of anthrax infections.

New Molecular Diagnostic Methods

New diagnostic techniques have focused on the use of the polymerase chain reaction to amplify markers specific to B. anthracis or the B. cereus group. Two markers, vrrA 89 and Ba813,90-92 have been the subject of extensive study. Other methods using the polymerase chain reaction to amplify specific virulence plasmid markers harbored by different anthrax strains may soon become available.56,93-96 These new rapid methods may become useful in the clinical setting, where early diagnosis is crucial.

Prevention and Treatment

Prophylaxis, Vaccination, and Decontamination

Prophylaxis for asymptomatic patients with suspected exposure to anthrax spores can be achieved with a six-week course of doxycycline or ciprofloxacin. If the suspected dose of spores is high, a longer course of antibiotics is warranted. Extended treatment is needed for total pulmonary clearance of spores, which are not affected by the presence of antibiotics.63,97

The standard anthrax vaccine in the United States is approved by the Food and Drug Administration and is routinely administered to persons at risk for exposure to anthrax spores. The existing supplies are currently being used to immunize all military personnel. Designated “anthrax vaccine adsorbed” (AVA), it is an aluminum hydroxide–precipitated preparation of protective antigen from attenuated, nonencapsulated B. anthracis cultures of the Sterne strain.98,99 Two inoculations with AVA afforded substantial protection against inhalational anthrax in rhesus monkeys,100 and a limited trial of a similar vaccine in humans indicated that it afforded considerable protection against cutaneous anthrax.101 AVA is administered subcutaneously in a 0.5-ml dose that is repeated at 2 and 4 weeks and at 6, 12, and 18 months.102 Boosters are then given annually. For those receiving antibiotic prophylaxis for suspected exposure, AVA may be given concurrently. There is a need for vaccines with better protection and a simpler schedule. Vaccines now being tested include preparations of protective antigen subunits with different adjuvants, protective antigen purified from recombinant sources, and live vaccines based on anthrax strains with auxotrophic mutations.103-113 Live attenuated endospore-based vaccines were widely used in the Soviet Union for both humans and livestock and remain in use in the Russian Federation today.103 The ability of any vaccine to protect humans in the event of aerosol attack, as in biologic terrorism or warfare, cannot be tested directly and therefore must remain a concern.114

A textile mill contaminated with anthrax spores was decontaminated with vaporized formaldehyde,115 and soil decontamination at Gruinard Island was achieved with formaldehyde in seawater.116 Although decontamination is desirable, the risk that resuspension of a deposited aerosol will lead to inhalational anthrax is much less than the risk due to a primary aerosol.117,118 Autoclaving and incineration are acceptable procedures for the decontamination of laboratory materials.

Treatment

Antibiotics

Table 2Table 2Pharmacologic Therapy for Bacillus anthracis Infection and Its Sequelae. summarizes pharmacologic therapy for anthrax. Penicillin and doxycycline are used for the treatment of anthrax. Intravenous administration is recommended in cases of inhalational, gastrointestinal, and meningeal anthrax. Cutaneous anthrax with signs of systemic involvement, extensive edema, or lesions on the head and neck also requires intravenous therapy. Streptomycin had a synergistic effect with penicillin in experiments and may also be given for inhalational anthrax. Despite early and vigorous treatment, the prognosis of patients with inhalational, gastrointestinal, or meningeal anthrax remains poor. Antibiotic therapy should be continued for at least 14 days after symptoms abate.67,78 In cutaneous anthrax, treatment with oral penicillin renders lesions sterile after 24 hours, although they still progress to eschar formation. Chloramphenicol, erythromycin, tetracycline, or ciprofloxacin can be administered to patients who are allergic to penicillin. If resistance to penicillin and doxycycline is suspected and antibiotic-susceptibility data are not available, ciprofloxacin may be administered empirically. Doxycycline and tetracycline are not recommended for pregnant women or children, and the effects of ciprofloxacin in pregnant women have not been determined.4

For culturing cutaneous lesions, gentle sampling with a moist, sterile applicator is preferred. Excision of the eschar is contraindicated and might hasten systemic dissemination. Lesions should be covered with sterile dressings that are changed regularly. Soiled dressings should be autoclaved and properly disposed of. In cases of extensive edema, meningitis, or swelling in the head-and-neck region, corticosteroid therapy should be initiated.119,120 Supportive therapy should be initiated to prevent septic shock and fluid and electrolyte imbalance, and to maintain airway patency.

Potential New Treatments

The current understanding that anthrax is a toxigenic condition suggests the potential of antitoxin therapy. The central importance of lethal toxin is supported by much research. Early experiments in which antibiotics were administered to animals at different stages of infection found a principle of “no return”; once the infection had reached a certain point, the animal was doomed, even after removal of the microbes. Test animals injected intravenously with purified lethal toxin died in a manner very similar to that of animals that died of the natural infection.3,15,19 Lethal-toxin–deficient strains are highly attenuated.121,122 Prior immunity (passive or active) to the lethal-toxin proteins protects animals from endospore challenge.63,123 Finally, toxin-affected macrophages produce the proinflammatory cytokines that mediate the shock and sudden death that occur in anthrax.3,15,19 Unfortunately, antitoxin preparations are not currently available in the United States. In addition, the recent discovery that lethal toxin acts as a zinc metalloprotease inside target cells and the identification of potential target substrates may provide new insights for use in designing drugs that directly inhibit the toxicity of lethal factor in vivo.14,17,18

Future Challenges

Anthrax holds an important place in the development of modern medicine and has long been intertwined with human history. Anthrax is believed to have been one of the Egyptian plagues at the time of Moses, and cases were clearly recorded by the ancient Romans.124 The anthrax bacillus was the model first used in the development of Koch's postulates and is considered the first “germ” proved to cause human disease.125 Pasteur later generated a capsule-null anthrax strain that was the first vaccine made from live attenuated bacteria for use in humans.126 At the birth of cellular immunology, Metchnikoff used the anthrax bacillus to examine the ability of his newly discovered macrophages to kill microbes.127 Today, investigators are using B. anthracis and its toxins in an attempt to understand early events in the infectious process and the molecular basis of inflammation.3,15,19

Unfortunately, new issues have arisen beyond those related to scientific inquiry. No casualty-producing terrorist use of anthrax has occurred, and the Federal Bureau of Investigation has stated that it has “no intelligence that state sponsors of terrorism, international terrorist groups, or domestic terrorist groups are currently planning to use these deadly weapons in the United States.”128 However, the incidence of hoaxes has greatly increased with recent publicity about anthrax, providing a challenge to law enforcement.129 Recent revelations regarding the development of anthrax weapons by the former Soviet Union and by Iraq, and of attempts to develop such weapons by the Aum Shinrikyo cult in Japan, make the potential use of B. anthracis in biologic terrorism a legitimate concern.4,129 New strains resistant to antibiotics or containing additional virulence factors could be misused with the intent of confounding treatment or prophylaxis.114,130 Whether our medical system would be able to provide appropriate prophylaxis and therapy in the event of a large-scale exposure to pathogenic endospores remains uncertain, even doubtful. It has now become relevant for physicians to refamiliarize themselves with clinical anthrax.

Supported in part by grants (AI-08649 and AI-40644) and a Medical Scientist Training award from the National Institutes of Health, by a grant (IRG-158 K) from the American Cancer Society, and by Duke University Medical Center.

We are indebted to Arthur Friedlander, M.D., Julia Chosy, Tanya Dixon, John Ireland, Matthew Weiner, and Kenneth Alexander, M.D., Ph.D., for their reading and critical discussion of the manuscript.

Source Information

From the Department of Microbiology, Duke University Medical Center, Durham, N.C. (T.C.D., P.C.H.); the Department of Molecular and Cellular Biology, Harvard University, Cambridge, Mass. (M.M.); the Department of Sociology, Boston College, Chestnut Hill, Mass. (J.G.); and the Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor (P.C.H.).

Address reprint requests to Dr. Hanna at 1150 W Medical, 5641 MS II, Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48104, or at dixont@umich.edu.

References

References

1. 1

   Hanna P. Anthrax pathogenesis and host response. Curr Top Microbiol Immunol 1998;225:13-35
   CrossRef | Web of Science | Medline

2. 2

   Meselson M, Guillemin J, Hugh-Jones M, et al. The Sverdlovsk anthrax outbreak of 1979. Science 1994;266:1202-1208
   CrossRef | Web of Science | Medline

3. 3

   Hanna PC, Acosta D, Collier RJ. On the role of macrophages in anthrax. Proc Natl Acad Sci U S A 1993;90:10198-10201
   CrossRef | Web of Science | Medline

4. 4

   Inglesby TV, Henderson DA, Bartlett JG, et al. Anthrax as a biological weapon: medical and public health management. JAMA 1999;281:1735-1745
   CrossRef | Web of Science | Medline

5. 5

   Watson A, Keir D. Information on which to base assessments of risk from environments contaminated with anthrax spores. Epidemiol Infect 1994;113:479-490
   CrossRef | Web of Science | Medline

6. 6

   Harris SH. Factories of death: Japanese secret biological warfare, 1932-1945, and the American cover-up. London: Routledge, 1994.
   

7. 7

   Ross JM. The pathogenesis of anthrax following the administration of spores by the respiratory route. J Pathol Bacteriol 1957;73:485-494
   CrossRef | Web of Science

8. 8

   Guidi-Rontani C, Weber-Levy M, Labruyere E, Mock M. Germination of Bacillus anthracis spores within alveolar macrophages. Mol Microbiol 1999;31:9-17
   CrossRef | Web of Science | Medline

9. 9

   Leppla SH. The anthrax toxin complex. In: Alouf J, Freer JH, eds. Sourcebook of bacterial protein toxins. London: Academic Press, 1991:277-302.
   

10. 10

    Leppla SH. Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells. Proc Natl Acad Sci U S A 1982;79:3162-3166
    CrossRef | Web of Science | Medline

11. 11

    Leppla SH. Bacillus anthracis calmodulin-dependent adenylate cyclase: chemical and enzymatic properties and interactions with eucaryotic cells. Adv Cyclic Nucleotide Protein Phosphorylation Res 1984;17:189-198
    Medline

12. 12

    O'Brien J, Friedlander A, Dreier T, Ezzell J, Leppla S. Effects of anthrax toxin components on human neutrophils. Infect Immun 1985;47:306-310
    Web of Science | Medline

13. 13

    Alexeyev OA, Morozov VG, Suzdaltseva TV, Mishukov AS, Steinberg LA. Impaired neutrophil function in the cutaneous form of anthrax. Infection 1994;22:281-282
    CrossRef | Web of Science | Medline

14. 14

    Hammond SE, Hanna PC. Lethal factor active-site mutations affect catalytic activity in vitro. Infect Immun 1998;66:2374-2378
    Web of Science | Medline

15. 15

    Hanna PC, Kruskal BA, Ezekowitz RA, Bloom BR, Collier RJ. Role of macrophage oxidative burst in the action of anthrax lethal toxin. Mol Med 1994;1:7-18
    Web of Science | Medline

16. 16

    Klimpel KR, Arora N, Leppla SH. Anthrax toxin lethal factor contains a zinc metalloprotease consensus sequence which is required for lethal toxin activity. Mol Microbiol 1994;13:1093-1100
    CrossRef | Web of Science | Medline

17. 17

    Duesbery NS, Webb CP, Leppla SH, et al. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science 1998;280:734-737
    CrossRef | Web of Science | Medline

18. 18

    Vitale G, Pellizzari R, Recchi C, Napolitani G, Mock M, Montecucco C. Anthrax lethal factor cleaves the N-terminus of MAPKKs and induces tyrosine/threonine phosphorylation of MAPKs in cultured macrophages. Biochem Biophys Res Commun 1998;248:706-711
    CrossRef | Web of Science | Medline

19. 19

    Hanna PC, Kochi S, Collier RJ. Biochemical and physiological changes induced by anthrax lethal toxin in J774 macrophage-like cells. Mol Biol Cell 1992;3:1269-1277
    Web of Science | Medline

20. 20

    Makino S-I, Uchida I, Terakado N, Sasakawa C, Yoshikawa M. Molecular characterization and protein analysis of the cap region, which is essential for encapsulation in Bacillus anthracis. J Bacteriol 1989;171:722-730
    Web of Science | Medline

21. 21

    Makino S, Sasakawa C, Uchida I, Terakado N, Yoshikawa M. Cloning and CO₂-dependent expression of the genetic region for encapsulation from Bacillus anthracis. Mol Microbiol 1988;2:371-376
    CrossRef | Web of Science | Medline

22. 22

    Dai Z, Sirard J-C, Mock M, Koehler TM. The atxA gene product activates transcription of the anthrax toxin genes and is essential for virulence. Mol Microbiol 1995;16:1171-1181
    CrossRef | Web of Science | Medline

23. 23

    Dai Z, Koehler TM. Regulation of anthrax toxin activator gene (atxA) expression in Bacillus anthracis: temperature, not CO2/bicarbonate, affects AtxA synthesis. Infect Immun 1997;65:2576-2582
    Web of Science | Medline

24. 24

    Uchida I, Hornung JM, Thorne CB, Klimpel KR, Leppla SH. Cloning and characterization of a gene whose product is a trans-activator of anthrax toxin synthesis. J Bacteriol 1993;175:5329-5338
    Web of Science | Medline

25. 25

    Uchida I, Makino S, Sekizaki T, Terakado N. Cross-talk to the genes for Bacillus anthracis capsule synthesis by atxA, the gene encoding the trans-activator of anthrax toxin synthesis. Mol Microbiol 1997;23:1229-1240
    CrossRef | Web of Science | Medline

26. 26

    Vietri NJ, Marrero R, Hoover TA, Welkos SL. Identification and characterization of a trans-activator involved in the regulation of encapsulation by Bacillus anthracis. Gene 1995;152:1-9
    CrossRef | Web of Science | Medline

27. 27

    Taylor JP, Dimmitt DC, Ezzell JW, Whitford H. Indigenous human cutaneous anthrax in Texas. South Med J 1993;86:1-4
    CrossRef | Web of Science | Medline

28. 28

    Human cutaneous anthrax -- North Carolina, 1987Arch Dermatol 1988;124:1324-1324
    CrossRef | Medline

29. 29

    Leads from the MMWR: human cutaneous anthrax -- North Carolina, 1987JAMA 1988;260:616-616
    CrossRef

30. 30

    Human cutaneous anthrax -- North Carolina, 1987MMWR Morb Mortal Wkly Rep 1988;37:413-414
    Medline

31. 31

    Bradaric N, Punda-Polic V. Cutaneous anthrax due to penicillin-resistant Bacillus anthracis transmitted by an insect bite. Lancet 1992;340:306-307
    CrossRef | Web of Science | Medline

32. 32

    Turell MJ, Knudson GB. Mechanical transmission of Bacillus anthracis by stable flies (Stomoxys calcitrans) and mosquitoes (Aedes aegypti and Aedes taeniorhynchus). Infect Immun 1987;55:1859-1861
    Web of Science | Medline

33. 33

    Smego RA Jr, Gebrian B, Desmangels G. Cutaneous manifestations of anthrax in rural Haiti. Clin Infect Dis 1998;26:97-102
    CrossRef | Web of Science | Medline

34. 34

    Edwards MS. Anthrax. In: Feigin RD, Cherry JD, eds. Textbook of pediatric infectious diseases. 3rd ed. Vol. 1. Philadelphia: W.B. Saunders, 1992:1053-6.
    

35. 35

    Doganay M, Bakir M, Dokmetas I. A case of cutaneous anthrax with toxaemic shock. Br J Dermatol 1987;117:659-662
    CrossRef | Web of Science | Medline

36. 36

    Kutluk MT, Secmeer G, Kanra G, Celiker A, Aksoyek H. Cutaneous anthrax. Cutis 1987;40:117-118
    Web of Science | Medline

37. 37

    Doganay M, Aygen B, Inan M, Kandemir O, Turnbull P. Temporal artery inflammation as a complication of anthrax. J Infect 1994;28:311-314
    CrossRef | Web of Science | Medline

38. 38

    Yorston D, Foster A. Cutaneous anthrax leading to corneal scarring from cicatricial ectropion. Br J Ophthalmol 1989;73:809-811
    CrossRef | Web of Science | Medline

39. 39

    Mallon E, McKee PH. Extraordinary case report: cutaneous anthrax. Am J Dermatopathol 1997;19:79-82
    CrossRef | Web of Science | Medline

40. 40

    LaForce FM. Anthrax. Clin Infect Dis 1994;19:1009-1014
    CrossRef | Web of Science | Medline

41. 41

    de Lalla F, Ezzell JW, Pellizzer G, et al. Familial outbreak of agriculture anthrax in an area of northern Italy. Eur J Clin Microbiol Infect Dis 1992;11:839-842
    CrossRef | Web of Science | Medline

42. 42

    Batykin V, Vygodchikov G, Sazshina Y. Outbreak of intestinal anthrax in Yarolslavl. J Hyg Epidemiol 1929;1:25-30
    

43. 43

    Dutz W, Kohout E. Anthrax. Pathol Annu 1971;6:209-248
    Medline

44. 44

    Dutz W, Saidi F, Kohout E. Gastric anthrax with massive ascites. Gut 1970;11:352-354
    CrossRef | Web of Science | Medline

45. 45

    Dutz W, Kohout-Dutz E. Anthrax. Int J Dermatol 1981;20:203-206
    CrossRef | Web of Science | Medline

46. 46

    Nalin DR, Sultana B, Sahunja R, et al. Survival of a patient with intestinal anthrax. Am J Med 1977;62:130-132
    CrossRef | Web of Science | Medline

47. 47

    Paulet R, Caussin C, Coudray JM, Selcer D, de Rohan Chabot P. Forme viscérale de charbon humain importée d'Africa. Presse Med 1994;23:477-478
    Web of Science | Medline

48. 48

    Alizad A, Ayoub EM, Makki N. Intestinal anthrax in a two-year-old child. Pediatr Infect Dis J 1995;14:394-395
    CrossRef | Web of Science | Medline

49. 49

    Dahlgren CM, Buchanan LM, Decker HM, Freed SW, Phillips CR, Brachman PS. Bacillus anthracis aerosols in goat hair processing mills. Am J Hyg 1960;72:24-31
    Web of Science | Medline

50. 50

    Albrink WS, Brooks SM, Biron RE, Kopel M. Human inhalation anthrax: a report of three fatal cases. Am J Pathol 1960;36:457-471
    Web of Science | Medline

51. 51

    Brachman PS, Kaufman AF, Dalldorf FG. Industrial inhalation anthrax. Bacteriol Rev 1966;30:646-659
    Web of Science | Medline

52. 52

    Manchee RJ, Broster MG, Henstridge RM, Stagg AJ, Melling J. Anthrax island. Nature 1982;296:598-598
    CrossRef | Web of Science | Medline

53. 53

    Manchee RJ. Bacillus anthracis on Gruinard Island. Nature 1981;294:254-255
    CrossRef | Web of Science | Medline

54. 54

    Sterne M. Anthrax island. Nature 1982;295:362-362
    CrossRef | Web of Science | Medline

55. 55

    Wynn J. Anthrax island: why worry? Nature 1982;298:506-507
    Web of Science | Medline

56. 56

    Jackson PJ, Hugh-Jones ME, Adair DM, et al. PCR analysis of tissue samples from the 1979 Sverdlovsk anthrax victims: the presence of multiple Bacillus anthracis strains in different victims. Proc Natl Acad Sci U S A 1998;95:1224-1229
    CrossRef | Web of Science | Medline

57. 57

    Guillemin J. Anthrax: the investigation of a deadly outbreak. Berkeley: University of California Press (in press).
    

58. 58

    Abramova FA, Grinberg LM, Yampolskaya OV, Walker DH. Pathology of inhalational anthrax in 42 cases from the Sverdlovsk outbreak of 1979. Proc Natl Acad Sci U S A 1993;90:2291-2294
    CrossRef | Web of Science | Medline

59. 59

    Penn CC, Klotz SA. Anthrax pneumonia. Semin Respir Infect 1997;12:28-30
    Medline

60. 60

    Brachman PS. Inhalation anthrax. Ann N Y Acad Sci 1980;353:83-93
    CrossRef | Medline

61. 61

    Brachman PS. Anthrax. Ann N Y Acad Sci 1970;174:577-582
    CrossRef | Web of Science | Medline

62. 62

    Albrink WS. Pathogenesis of inhalation anthrax. Bacteriol Rev 1961;25:268-273
    Web of Science | Medline

63. 63

    Friedlander AM, Welkos SL, Pitt ML, et al. Postexposure prophylaxis against experimental inhalation anthrax. J Infect Dis 1993;167:1239-1243
    CrossRef | Web of Science | Medline

64. 64

    Henderson DW, Peacock S, Belton FC. Observations on the prophylaxis of experimental pulmonary anthrax in the monkey. J Hyg (Lond) 1956;54:28-36
    CrossRef | Medline

65. 65

    Tahernia AC, Hashemi G. Survival in anthrax meningitis. Pediatrics 1972;50:329-333
    Web of Science | Medline

66. 66

    Tabatabaie P, Syadati A. Bacillus anthracis as a cause of bacterial meningitis. Pediatr Infect Dis J 1993;12:1035-1037
    CrossRef | Web of Science | Medline

67. 67

    Tahernia AC. Treatment of anthrax in children. Arch Dis Child 1967;42:181-182
    CrossRef | Web of Science | Medline

68. 68

    Rangel RA, Gonzalez DA. Bacillus anthracic meningitis. Neurology 1975;25:525-530
    Web of Science | Medline

69. 69

    Pluot M, Vital C, Aubertin J, Croix JC, Pire JC, Poisot D. Anthrax meningitis: report of two cases with autopsies. Acta Neuropathol (Berl) 1976;36:339-345
    CrossRef | Web of Science | Medline

70. 70

    Aksaray N, Cinaz P, Coskun U, Serbest M, Koksal F. Cutaneous anthrax. Trop Geogr Med 1990;42:168-171
    Medline

71. 71

    Wheat J. Histoplasma. In: Gorbach SL, Bartlett JG, Blacklow NR, eds. Infectious diseases. 2nd ed. Philadelphia: W.B. Saunders, 1998:2335-44.
    

72. 72

    Claus D, Berkeley RCW. Genus Bacillus. In: Sneath PHA, ed. Bergey's manual of systematic bacteriology. Vol. 2. Baltimore: Williams & Wilkins, 1986:1105-39.
    

73. 73

    Turnbull PCB, Kramer JM. Bacillus. In: Balows A, ed. Manual of clinical microbiology. 5th ed. Washington, D.C.: American Society for Microbiology, 1991:296-303.
    

74. 74

    Penn CC, Klotz SA. Bacillus anthracis and other aerobic spore formers. In: Gorbach SL, Bartlett JG, Blacklow NR, eds. Infectious diseases. 2nd ed. Philadelphia: W.B. Saunders, 1998:1747-50.
    

75. 75

    Parry JM, Turnbull PCB, Gibson JR. A color atlas of Bacillus species. London: Wolfe Medical, 1983:272.
    

76. 76

    Green BD, Battisti L, Koehler TM, Thorne CB, Ivins BE. Demonstration of a capsule plasmid in Bacillus anthracis. Infect Immun 1985;49:291-297
    Web of Science | Medline

77. 77

    Penn CC, Klotz SA. Anthrax. In: Gorbach SL, Bartlett JG, Blacklow NR, eds. Infectious diseases. 2nd ed. Philadelphia: W.B. Saunders, 1998:1575-8.
    

78. 78

    Gold H. Treatment of anthrax. Fed Proc 1967;26:1563-1568
    Medline

79. 79

    Knisely RF. Selective medium for Bacillus anthracis. J Bacteriol 1966;92:784-786
    Web of Science | Medline

80. 80

    Logan NA, Carman JA, Melling J, Berkeley RCW. Identification of Bacillus anthracis by API tests. J Med Microbiol 1985;20:75-85
    CrossRef | Web of Science | Medline

81. 81

    Shlyakhov E, Rubinstein E. Evaluation of the anthraxin skin test for diagnosis of acute and past human anthrax. Eur J Clin Microbiol Infect Dis 1996;15:242-245
    CrossRef | Web of Science | Medline

82. 82

    Lalitha MK, Thomas MK. Penicillin resistance in Bacillus anthracis. Lancet 1997;349:1522-1522
    CrossRef | Web of Science | Medline

83. 83

    Harrison LH, Ezzell JW, Abshire TG, Kidd S, Kaufmann AF. Evaluation of serologic tests for diagnosis of anthrax after an outbreak of cutaneous anthrax in Paraguay. J Infect Dis 1989;160:706-710
    CrossRef | Web of Science | Medline

84. 84

    Turnbull PC, Doganay M, Lindeque PM, Aygen B, McLaughlin J. Serology and anthrax in humans, livestock and Etosha National Park wildlife. Epidemiol Infect 1992;108:299-313
    CrossRef | Web of Science | Medline

85. 85

    Sirisanthana T, Nelson KE, Ezzell JW, Abshire TG. Serological studies of patients with cutaneous and oral-oropharyngeal anthrax from northern Thailand. Am J Trop Med Hyg 1988;39:575-581
    Web of Science | Medline

86. 86

    Johnson-Winegar A. Comparison of enzyme-linked immunosorbent and indirect hemagglutination assays for determining anthrax antibodies. J Clin Microbiol 1984;20:357-361
    Web of Science | Medline

87. 87

    Pfisterer RM. Eine Milzbrandepidemie in der Schweiz: Klinische, diagnostische und epidemiologische Aspekte einer weitgehend vergessenen Krankheit. Schweiz Med Wochenschr 1991;121:813-825
    Medline

88. 88

    Shlyakhov E, Rubinstein E, Novikov I. Anthrax post-vaccinal cell-mediated immunity in humans: kinetics pattern. Vaccine 1997;15:631-636
    CrossRef | Web of Science | Medline

89. 89

    Andersen GL, Simchock JM, Wilson KH. Identification of a region of genetic variability among Bacillus anthracis strains and related species. J Bacteriol 1996;178:377-384
    Web of Science | Medline

90. 90

    Patra G, Vaissaire J, Weber-Levy M, Le Doujet C, Mock M. Molecular characterization of Bacillus strains involved in outbreaks of anthrax in France in 1997. J Clin Microbiol 1998;36:3412-3414
    Web of Science | Medline

91. 91

    Patra G, Sylvestre P, Ramisse V, Therasse J, Guesdon JL. Isolation of a specific chromosomic DNA sequence of Bacillus anthracis and its possible use in diagnosis. FEMS Immunol Med Microbiol 1996;15:223-231
    CrossRef | Web of Science | Medline

92. 92

    Ramisse V, Patra G, Garrigue H, Guesdon JL, Mock M. Identification and characterization of Bacillus anthracis by multiplex PCR analysis of sequences on plasmids pXO1 and pXO2 and chromosomal DNA. FEMS Microbiol Lett 1996;145:9-16
    CrossRef | Web of Science | Medline

93. 93

    Keim P, Kalif A, Schupp J, et al. Molecular evolution and diversity in Bacillus anthracis as detected by amplified fragment length polymorphism markers. J Bacteriol 1997;179:818-824
    Web of Science | Medline

94. 94

    Klevytskya A, Schupp J, Price LB, et al. A multiplexed fluorescent PCR genotyping system based on ten highly informative single-locus markers for B. anthracis strain identification. Presented at the Third International Conference on Anthrax, Plymouth, England, 1998. abstract.
    

95. 95

    Price LB, Hugh-Jones M, Jackson PJ, Keim P. Genetic diversity in the protective antigen gene of Bacillus anthracis. J Bacteriol 1999;181:2358-2362
    Web of Science | Medline

96. 96

    Jackson PJ, Walthers EA, Kalif AS, et al. Characterization of the variable-number tandem repeats in vrrA from different Bacillus anthracis isolates. Appl Environ Microbiol 1997;63:1400-1405
    Web of Science | Medline

97. 97

    Vancurik J. Causes of the failure of antibiotic prophylaxis of inhalation anthrax and clearance of the spores from the lungs. Folia Microbiol (Praha) 1966;11:459-464
    CrossRef | Web of Science | Medline

98. 98

    Vaccine against anthraxBMJ 1965;5464:717-718
    

99. 99

    Anthrax vaccineMed Lett Drugs Ther 1998;40:52-53
    Web of Science | Medline

100. 100

     Ivins BE, Fellows P, Pitt ML, et al. Efficacy of standard human anthrax vaccine against Bacillus anthracis aerosol spore challenge in rhesus monkeys. Salisbury Med Bull 1996;87:125-126
     

101. 101

     Brachman PS, Gold H, Plotkin SA, Fekety FR, Werrin M, Ingraham NR. Field evaluation of a human anthrax vaccine. Am J Public Health 1962;52:632-645
     CrossRef | Web of Science

102. 102

     Franz DR, Jahrling PB, Friedlander AM, et al. Clinical recognition and management of patients exposed to biological warfare agents. JAMA 1997;278:399-411
     CrossRef | Web of Science | Medline

103. 103

     Shlyakhov EN, Rubinstein E. Human live anthrax vaccine in the former USSR. Vaccine 1994;12:727-730
     CrossRef | Web of Science | Medline

104. 104

     Pezard C, Weber M, Sirard JC, Berche P, Mock M. Protective immunity induced by Bacillus anthracis toxin-deficient strains. Infect Immun 1995;63:1369-1372
     Web of Science | Medline

105. 105

     Pezard C, Sirard JC, Mock M. Protective immunity induced by Bacillus anthracis toxin mutant strains. Adv Exp Med Biol 1996;397:69-72
     Medline

106. 106

     Miller J, McBride BW, Manchee RJ, Moore P, Baillie LW. Production and purification of recombinant protective antigen and protective efficacy against Bacillus anthracis. Lett Appl Microbiol 1998;26:56-60
     CrossRef | Web of Science | Medline

107. 107

     Little SF, Knudson GB. Comparative efficacy of Bacillus anthracis live spore vaccine and protective antigen vaccine against anthrax in the guinea pig. Infect Immun 1986;52:509-512
     Web of Science | Medline

108. 108

     Ivins BE, Welkos SL, Knudson GB, Little SF. Immunization against anthrax with aromatic compound-dependent (Aro-) mutants of Bacillus anthracis and with recombinant strains of Bacillus subtilis that produce anthrax protective antigen. Infect Immun 1990;58:303-308
     Web of Science | Medline

109. 109

     Ivins BE, Welkos SL, Little SF, Crumrine MH, Nelson GO. Immunization against anthrax with Bacillus anthracis protective antigen combined with adjuvants. Infect Immun 1992;60:662-668
     Web of Science | Medline

110. 110

     Ivins BE, Fellows PF, Nelson GO. Efficacy of a standard human anthrax vaccine against Bacillus anthracis spore challenge in guinea-pigs. Vaccine 1994;12:872-874
     CrossRef | Web of Science | Medline

111. 111

     Coulson NM, Fulop M, Titball RW. Bacillus anthracis protective antigen, expressed in Salmonella typhimurium SL 3261, affords protection against anthrax spore challenge. Vaccine 1994;12:1395-1401
     CrossRef | Web of Science | Medline

112. 112

     Baillie L, Moir A, Manchee R. The expression of the protective antigen of Bacillus anthracis in Bacillus subtilis. J Appl Microbiol 1998;84:741-746
     CrossRef | Web of Science | Medline

113. 113

     Baillie LW, Moore P, McBride BW. A heat-inducible Bacillus subtilis bacteriophage phi 105 expression system for the production of the protective antigen of Bacillus anthracis. FEMS Microbiol Lett 1998;163:43-47
     Web of Science | Medline

114. 114

     Hanna P. How anthrax kills. Science 1998;280:1671, 1673-1671, 1674
     CrossRef | Web of Science

115. 115

     Young LS, Feeley JC, Brachman PS. Vaporized formaldehyde treatment of a textile mill contaminated with Bacillus anthracis. Arch Environ Health 1970;20:400-403
     Medline

116. 116

     Manchee RJ, Broster MG, Stagg AJ, Hibbs SE. Formaldehyde dilution effectively inactivates spores of Bacillus anthracis on the Scottish island of Gruinard. Appl Environ Microbiol 1994;60:4167-4171
     Web of Science | Medline

117. 117

     Birensvige A. Inhalation hazard from reaerosolized biological agents: a review. Aberdeen, Md.: Army Chemical Research, Development and Engineering Center, 1992.
     

118. 118

     Davids DE, Lejeune AR. Secondary aerosol hazard in the field. Raulston, Alta.: Suffield Defence Research Establishment, 1981.
     

119. 119

     Knudson GB. Treatment of anthrax in man: history and current concepts. Mil Med 1986;151:71-77
     Web of Science | Medline

120. 120

     Doust JY, Sarkarzadeh A, Kavoossi K. Corticosteroid in treatment of malignant edema of chest wall and neck (anthrax). Dis Chest 1968;53:773-774
     CrossRef | Medline

121. 121

     Cataldi A, Labruyere E, Mock M. Construction and characterization of a protective antigen-deficient Bacillus anthracis strain. Mol Microbiol 1990;4:1111-1117
     CrossRef | Web of Science | Medline

122. 122

     Pezard C, Berche P, Mock M. Contribution of individual toxin components to virulence of Bacillus anthracis. Infect Immun 1991;59:3472-3477
     Web of Science | Medline

123. 123

     Turnbull PC, Leppla SH, Broster MG, Quinn CP, Melling J. Antibodies to anthrax toxin in humans and guinea pigs and their relevance to protective immunity. Med Microbiol Immunol (Berl) 1988;177:293-303
     CrossRef | Web of Science | Medline

124. 124

     Dirckx JH. Virgil on anthrax. Am J Dermatopathol 1981;3:191-195
     CrossRef | Web of Science | Medline

125. 125

     Koch R. The aetiology of anthrax based on the ontogeny of the anthrax bacillus. Beitr Biol Pflanz 1877;2:277-282
     

126. 126

     Pasteur L. De l'atténuation des virus et de leur retour à la virulence. C R Acad Sci III 1881;92:429-435
     

127. 127

     Metchnikoff E. Immunity in infective diseases. Cambridge, England: Cambridge University Press, 1905.
     

128. 128

     Ember LR. Bioterrorism: combating the threat. Chem Eng News 1999;77:8-17
     Web of Science

129. 129

     Bioterrorism alleging use of anthrax and interim guidelines for management -- United States, 1998. MMWR Morb Mortal Wkly Rep 1999;48:69-74
     Medline

130. 130

     Pomerantsev AP, Staritsin NA, Mockov Yu V, Marinin LI. Expression of cereolysine AB genes in Bacillus anthracis vaccine strain ensures protection against experimental hemolytic anthrax infection. Vaccine 1997;15:1846-1850
     CrossRef | Web of Science | Medline

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14. 14

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15. 15

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16. 16

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22. 22

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23. 23

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    CrossRef

25. 25

    Sinan Akbayram, Murat Doğan, Cihangir Akgün, Erdal Peker, M. Selçuk Bektaş, Avni Kaya, Hüseyin Çaksen, Ahmet Faik Öner. (2010) Clinical Findings in Children with Cutaneous Anthrax in Eastern Turkey. Pediatric Dermatology 27:6, 600-606
    CrossRef

26. 26

    Irene Zornetta, Lucia Brandi, Blythe Janowiak, Federica Dal Molin, Fiorella Tonello, R. John Collier, Cesare Montecucco. (2010) Imaging the cell entry of the anthrax oedema and lethal toxins with fluorescent protein chimeras. Cellular Microbiology 12:10, 1435-1445
    CrossRef

27. 27

    S Ramasamy, CQ Liu, H Tran, A Gubala, P Gauci, J McAllister, T Vo. (2010) Principles of antidote pharmacology: an update on prophylaxis, post-exposure treatment recommendations and research initiatives for biological agents. British Journal of Pharmacology 161:4, 721-748
    CrossRef

28. 28

    Mehmet Doganay, Gokhan Metan, Emine Alp. (2010) A review of cutaneous anthrax and its outcome. Journal of Infection and Public Health 3:3, 98-105
    CrossRef

29. 29

    Fiona J. Sorrell, Gemma K. Greenwood, Kristian Birchall, Beining Chen. (2010) Development of a differential scanning fluorimetry based high throughput screening assay for the discovery of affinity binders against an anthrax protein. Journal of Pharmaceutical and Biomedical Analysis 52:5, 802-808
    CrossRef

30. 30

    Mansour Mohamadzadeh, Evelyn Durmaz, Mojgan Zadeh, Krishna Chaitanya Pakanati, Matthew Gramarossa, Valeria Cohran, Todd R Klaenhammer. (2010) Targeted expression of anthrax protective antigen by Lactobacillus gasseri as an anthrax vaccine. Future Microbiology 5:8, 1289-1296
    CrossRef

31. 31

    Fatma Sule Afsar. (2010) Skin infections in developing countries. Current Opinion in Pediatrics 22:4, 459-466
    CrossRef

32. 32

    Danil Dobrynin, Gregory Fridman, Yurii V Mukhin, Meghan A Wynosky-Dolfi, Judy Rieger, Richard F Rest, Alexander F Gutsol, Alexander Fridman. (2010) Cold Plasma Inactivation of Bacillus cereus and Bacillus anthracis (Anthrax) Spores. IEEE Transactions on Plasma Science 38:8, 1878-1884
    CrossRef

33. 33

    Lynne M. Shetron-Rama, Amy C. Herring-Palmer, Gary B. Huffnagle, Philip Hanna. (2010) Transport of Bacillus anthracis from the lungs to the draining lymph nodes is a rapid process facilitated by CD11c+ cells. Microbial Pathogenesis 49:1-2, 38-46
    CrossRef

34. 34

    Petros V. Gkazonis, Georgios A. Dalkas, Christos T. Chasapis, Alexios Vlamis-Gardikas, Detlef Bentrop, Georgios A. Spyroulias. (2010) Purification and biophysical characterization of the core protease domain of anthrax lethal factor. Biochemical and Biophysical Research Communications 396:3, 643-647
    CrossRef

35. 35

    D.S. King, V.A. Luna, A.C. Cannons, P.T. Amuso. (2010) Procurement of spore-free Bacillus anthracis for molecular typing outside of BSL3 environment. Journal of Applied Microbiology 108:5, 1817-1827
    CrossRef

36. 36

    Brian L. Bishop, James P. Lodolce, Lauren E. Kolodziej, David L. Boone, Wei Jen Tang. (2010) The role of anthrolysin O in gut epithelial barrier disruption during Bacillus anthracis infection. Biochemical and Biophysical Research Communications 394:2, 254-259
    CrossRef

37. 37

    R. J. Hay, B. M. Adriaans. 2010. Bacterial Infections. , 1-82.
    CrossRef

38. 38

    Elizabeth Ablah, Eileen Scanlon, Kurt Konda, Annie Tinius, Kristine M. Gebbie. (2010) A Large-Scale Points-of-Dispensing Exercise for First Responders and First Receivers in Nassau County, New York. Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science 8:1, 25-35
    CrossRef

39. 39

    Paul E. Carlson Jr, Shandee D. Dixon, Brian K. Janes, Katherine A. Carr, Tyler D. Nusca, Erica C. Anderson, Sarra E. Keene, David H. Sherman, Philip C. Hanna. (2010) Genetic analysis of petrobactin transport in Bacillus anthracis. Molecular Microbiology 75:4, 900-909
    CrossRef

40. 40

    Katherine A. Carr, Suzanne R. Lybarger, Erica C. Anderson, Brian K. Janes, Philip C. Hanna. (2010) The role of Bacillus anthracis germinant receptors in germination and virulence. Molecular Microbiology 75:2, 365-375
    CrossRef

41. 41

    R. J. Hay, H. R. Ashbee. 2010. , 1.
    CrossRef

42. 42

    Philippe Bossi. 2009. National and International Aspects on Bioterrorism and Biosecurity. .
    CrossRef

43. 43

    Pierre L. Goossens. (2009) Animal models of human anthrax: The Quest for the Holy Grail. Molecular Aspects of Medicine 30:6, 467-480
    CrossRef

44. 44

    Jean-Nicolas Tournier, Silvia Rossi Paccani, Anne Quesnel-Hellmann, Cosima T. Baldari. (2009) Anthrax toxins: A weapon to systematically dismantle the host immune defenses. Molecular Aspects of Medicine 30:6, 456-466
    CrossRef

45. 45

    Y. Kurosaki, T. Sakuma, A. Fukuma, Y. Fujinami, K. Kawamoto, N. Kamo, S.-I. Makino, J. Yasuda. (2009) A simple and sensitive method for detection of Bacillus anthracis by loop-mediated isothermal amplification. Journal of Applied Microbiology 107:6, 1947-1956
    CrossRef

46. 46

    Adam Driks. (2009) The Bacillus anthracis spore. Molecular Aspects of Medicine 30:6, 368-373
    CrossRef

47. 47

    Dimitrios G. Bouzianas. (2009) Medical countermeasures to protect humans from anthrax bioterrorism. Trends in Microbiology 17:11, 522-528
    CrossRef

48. 48

    Jihyun Yang, Sang Su Woo, Young Hee Ryu, Cheol-Heui Yun, Min-Hee Cho, Gi-Eun Rhie, Bong-Su Kim, Hee-Bok Oh, Seung Hyun Han. (2009) Bacillus anthracis lethal toxin attenuates lipoteichoic acid-induced maturation and activation of dendritic cells through a unique mechanism. Molecular Immunology 46:16, 3261-3268
    CrossRef

49. 49

    Georgios A. Dalkas, Athanasios Papakyriakou, Alexios Vlamis-Gardikas, Georgios A. Spyroulias. (2009) Insights into the anthrax lethal factor-substrate interaction and selectivity using docking and molecular dynamics simulations. Protein Science 18:8, 1774-1785
    CrossRef

50. 50

    Andreas V. Hadjinicolaou, Victoria L. Demetriou, Johana Hezka, Wolfgang Beyer, Ted L. Hadfield, Leondios G. Kostrikis. (2009) Use of molecular beacons and multi-allelic real-time PCR for detection of and discrimination between virulent Bacillus anthracis and other Bacillus isolates. Journal of Microbiological Methods 78:1, 45-53
    CrossRef

51. 51

    Martha Boss, Dennis Day, Charles Allen. 2009. Filtration. .
    CrossRef

52. 52

    Christopher Premanandan, Craig A. Storozuk, Corey D. Clay, Michael D. Lairmore, Larry S. Schlesinger, Andrew J. Phipps. (2009) Complement protein C3 binding to Bacillus anthracis spores enhances phagocytosis by human macrophages. Microbial Pathogenesis 46:6, 306-314
    CrossRef

53. 53

    Devin L. Stauff, Eric P. Skaar. (2009) Bacillus anthracis HssRS signalling to HrtAB regulates haem resistance during infection. Molecular Microbiology 72:3, 763-778
    CrossRef

54. 54

    Sarah Donegan, Richard Bellamy, Carrol L Gamble, Sarah Donegan. 2009. Vaccines for preventing anthrax. .
    CrossRef

55. 55

    Mehmet Doganay, Gokhan Metan. (2009) Human Anthrax in Turkey from 1990 to 2007. Vector-Borne and Zoonotic Diseases 9:2, 131-140
    CrossRef

56. 56

    Christian A. Schmittinger, Martin W. Dünser, Ganbat Tsenddorj. (2009) Norepinephrine in anthrax-associated shock: Even worse than figs?*. Critical Care Medicine 37:4, 1510-1513
    CrossRef

57. 57

    Sarah M Barry, Gregory L Challis. (2009) Recent advances in siderophore biosynthesis. Current Opinion in Chemical Biology 13:2, 205-215
    CrossRef

58. 58

    Te-Hui Liu, Jon Oscherwitz, Bruce Schnepp, Jana Jacobs, Fen Yu, Kemp B Cease, Philip R Johnson. (2009) Genetic Vaccines for Anthrax Based on Recombinant Adeno-associated Virus Vectors. Molecular Therapy 17:2, 373-379
    CrossRef

59. 59

    Stefan Richter, Valerie J. Anderson, Gabriella Garufi, Lianghua Lu, Jonathan M. Budzik, Andrzej Joachimiak, Chuan He, Olaf Schneewind, Dominique Missiakas. (2009) Capsule anchoring in Bacillus anthracis occurs by a transpeptidation reaction that is inhibited by capsidin. Molecular Microbiology 71:2, 404-420
    CrossRef

60. 60

    Leslie A. Dauphin, Benjamin D. Moser, Michael D. Bowen. (2009) Evaluation of five commercial nucleic acid extraction kits for their ability to inactivate Bacillus anthracis spores and comparison of DNA yields from spores and spiked environmental samples. Journal of Microbiological Methods 76:1, 30-37
    CrossRef

61. 61

    Monica Carrera, Jose-Luis Sagripanti. (2009) Artificial plasmid engineered to simulate multiple biological threat agents. Applied Microbiology and Biotechnology 81:6, 1129-1139
    CrossRef

62. 62

    Ping-Jen (Joe) Chou, Catherine A. Newton, Izabella Perkins, Herman Friedman, Thomas W. Klein. (2008) Suppression of Dendritic Cell Activation by Anthrax Lethal Toxin and Edema Toxin Depends on Multiple Factors Including Cell Source, Stimulus Used, and Function Tested. DNA and Cell Biology 27:12, 637-648
    CrossRef

63. 63

    David Vance, Mrinal Shah, Amit Joshi, Ravi S. Kane. (2008) Polyvalency: A promising strategy for drug design. Biotechnology and Bioengineering 101:3, 429-434
    CrossRef

64. 64

    Fatemeh Vahedi, Jennelle Kyd, Gholamreza Moazeni Jula, Monavvar Afzalaghaeei, Mahdi Kianizadeh, Mahmoud Mahmoudi. (2008) A DNA vaccine candidate for B. anthracis immunization, pcDNA3.1+PA plasmid, induce Th1/Th2 mixed responses and protection in mice. World Journal of Microbiology and Biotechnology 24:10, 2171-2178
    CrossRef

65. 65

    S.D. Klas, C.R. Petrie, S.J. Warwood, M.S. Williams, C.L. Olds, J.P. Stenz, A.M. Cheff, M. Hinchcliffe, C. Richardson, S. Wimer. (2008) A single immunization with a dry powder anthrax vaccine protects rabbits against lethal aerosol challenge. Vaccine 26:43, 5494-5502
    CrossRef

66. 66

    Andrew C. Hahn, C. Rick Lyons, Mary F. Lipscomb. (2008) Effect of Bacillus anthracis virulence factors on human dendritic cell activation. Human Immunology 69:9, 552-561
    CrossRef

67. 67

    Robert J. Cybulski, Patrick Sanz, Dennis McDaniel, Steve Darnell, Robert L. Bull, Alison D. O’Brien. (2008) Recombinant Bacillus anthracis spore proteins enhance protection of mice primed with suboptimal amounts of protective antigen. Vaccine 26:38, 4927-4939
    CrossRef

68. 68

    Wei-Gang Hu, Junfei Yin, Scott Jager, Christina Wong, Courtney Fulton, George A. Rayner, Connie Aw, Glen R. Fisher, Xiaojiang Dai, Les P. Nagata. (2008) A Novel Approach to Development of Monoclonal Antibodies Using Native Antigen for Immunization and Recombinant Antigen for Screening. Hybridoma 27:4, 307-311
    CrossRef

69. 69

    Sean V. Shadomy, Theresa L. Smith. (2008) Anthrax. Journal of the American Veterinary Medical Association 233:1, 63-72
    CrossRef

70. 70

    Scott Duncan, Jim Ho. (2008) Estimation of Viable Spores in Bacillus atrophaeus (BG) Particles of 1 to 9 μm Size Range. CLEAN - Soil, Air, Water 36:7, 584-592
    CrossRef

71. 71

    M. K. Karahocagil, N. Akdeniz, H. Akdeniz, Ö. Çalka, H. Karsen, A. Bilici, S. G. Bilgili, Ö. Evirgen. (2008) Cutaneous anthrax in Eastern Turkey: a review of 85 cases. Clinical and Experimental Dermatology 33:4, 406-411
    CrossRef

72. 72

    Tae Jin Kang, Subhendu Basu, Lei Zhang, Karen E. Thomas, Stefanie N. Vogel, Les Baillie, Alan S. Cross. (2008) Bacillus anthracis spores and lethal toxin induce IL-1β via functionally distinct signaling pathways. European Journal of Immunology 38:6, 1574-1584
    CrossRef

73. 73

    Beth L. Hahn, Timothy S. Bischof, Peter G. Sohnle. (2008) Superficial exudates of neutrophils prevent invasion of Bacillus anthracis bacilli into abraded skin of resistant mice. International Journal of Experimental Pathology 89:3, 180-187
    CrossRef

74. 74

    Christopher J. Watts, Beth L. Hahn, Peter G. Sohnle. (2008) Progressive and destructive hair follicle infections in a murine cutaneous anthrax model. Microbial Pathogenesis 44:5, 363-369
    CrossRef

75. 75

    Brandon D. Gaddis, Charles M. Rubert Pérez, Jean Chmielewski. (2008) Inhibitors of anthrax lethal factor based upon N-oleoyldopamine. Bioorganic & Medicinal Chemistry Letters 18:7, 2467-2470
    CrossRef

76. 76

    Chun-Qiang Liu, Stewart D. Nuttall, Hung Tran, Michelle Wilkins, Victor A. Streltsov, Malcolm R. Alderton. (2008) Construction, crystal structure and application of a recombinant protein that lacks the collagen-like region of BclA fromBacillus anthracis spores. Biotechnology and Bioengineering 99:4, 774-782
    CrossRef

77. 77

    Gregory J. Moran, David A. Talan, Fredrick M. Abrahamian. (2008) Biological Terrorism. Infectious Disease Clinics of North America 22:1, 145-187
    CrossRef

78. 78

    Laura M Zarebski, Kerrie Vaughan, John Sidney, Bjoern Peters, Howard Grey, Kim D Janda, Arturo Casadevall, Alessandro Sette. (2008) Analysis of epitope information related to Bacillus anthracis and Clostridium botulinum. Expert Review of Vaccines 7:1, 55-74
    CrossRef

79. 79

    S. Plotkin, J. D. Grabenstein. (2008) Countering Anthrax: Vaccines and Immunoglobulins. Clinical Infectious Diseases 46:1, 129-136
    CrossRef

80. 80

    Jim E Zeegelaar, William R Faber. (2008) Imported Tropical Infectious Ulcers in Travelers. American Journal of Clinical Dermatology 9:4, 219-232
    CrossRef

81. 81

    Yongxin Zhang, Jianxia Qiu, Yu Zhou, Farhang Farhangfar, Jenny Hester, Augustine Y. Lin, William K. Decker. (2008) Plasmid-based vaccination with candidate anthrax vaccine antigens induces durable type 1 and type 2 T-helper immune responses. Vaccine 26:5, 614-622
    CrossRef

82. 82

    Paul K. Muoria, Philip Muruthi, Waititu K. Kariuki, Boru A. Hassan, Dominic Mijele, Nicholas O. Oguge. (2007) Anthrax outbreak among Grevy's zebra (Equus grevyi) in Samburu, Kenya. African Journal of Ecology 45:4, 483-489
    CrossRef

83. 83

    Martha Triantafilou, Ahmed Uddin, Sebastien Maher, Nicholas Charalambous, Thomas S. C. Hamm, Ahmad Alsumaiti, Kathy Triantafilou. (2007) Anthrax toxin evades Toll-like receptor recognition, whereas its cell wall components trigger activation via TLR2/6 heterodimers. Cellular Microbiology 9:12, 2880-2892
    CrossRef

84. 84

    Sefer Kumandas, Mehmet Kose, Hakan Gumus, Huseyin Per, Berna Saygin. (2007) Cutaneous anthrax involving the genital area. Annals of Tropical Paediatrics: International Child Health 27:4, 307-309
    CrossRef

85. 85

    N. Declerck, L. Bouillaut, D. Chaix, N. Rugani, L. Slamti, F. Hoh, D. Lereclus, S. T. Arold. (2007) Structure of PlcR: Insights into virulence regulation and evolution of quorum sensing in Gram-positive bacteria. Proceedings of the National Academy of Sciences 104:47, 18490-18495
    CrossRef

86. 86

    Tom Jefferson, Ruth Foxlee, Chris Del Mar, Liz Dooley, Eliana Ferroni, Bill Hewak, Adi Prabhala, Sreekumaran Nair, Alessandro Rivetti, Tom Jefferson. 2007. Interventions for the interruption or reduction of the spread of respiratory viruses. .
    CrossRef

87. 87

    Jill Downing, Thomas W. Greig, Martin D. Quattlebaum, Manuel Valentin, Timothy C. Heeren, John D. Grabenstein. (2007) Assessing the Safety of Anthrax Immunization in US Army Aircrew Members via Physical Examination. Journal of Occupational and Environmental Medicine 49:10, 1079-1085
    CrossRef

88. 88

    Dennis M. Klinman, Debra Currie, Gloria Lee, Vanessa Grippe, Tod Merkel. (2007) Systemic but not mucosal immunity induced by AVA prevents inhalational anthrax. Microbes and Infection 9:12-13, 1478-1483
    CrossRef

89. 89

    Jun X. Wheeler, Gail Whiting, Sjoerd Rijpkema. (2007) Proteomic analysis of the response of the human neutrophil-like cell line NB-4 after exposure to anthrax lethal toxin. PROTEOMICS – CLINICAL APPLICATIONS 1:10, 1266-1279
    CrossRef

90. 90

    Amanda B. DuBois, Lucy C. Freytag, John D. Clements. (2007) Evaluation of combinatorial vaccines against anthrax and plague in a murine model. Vaccine 25:24, 4747-4754
    CrossRef

91. 91

    G.T. Vilas-Bôas, A.P.S. Peruca, O.M.N. Arantes. (2007) Biology and taxonomy of Bacillus cereus , Bacillus anthracis , and Bacillus thuringiensis. Canadian Journal of Microbiology 53:6, 673-687
    CrossRef

92. 92

    Russell L During, Bruce G Gibson, Wei Li, Ellen A Bishai, Gurjit S Sidhu, Jacques Landry, Frederick S Southwick. (2007) Anthrax lethal toxin paralyzes actin-based motility by blocking Hsp27 phosphorylation. The EMBO Journal 26:9, 2240-2250
    CrossRef

93. 93

    Jian Zhou, Guannan Wang, Li-He Zhang, Xin-Shan Ye. (2007) Modifications of aminoglycoside antibiotics targeting RNA. Medicinal Research Reviews 27:3, 279-316
    CrossRef

94. 94

    Timothy S. Bischof, Beth L. Hahn, Peter G. Sohnle. (2007) Experimental cutaneous Bacillus anthracis infections in hairless HRS/J mice. International Journal of Experimental Pathology 88:1, 75-84
    CrossRef

95. 95

    Mark I Hirsh, Irena Manov, Victoria Cohen-Kaplan, Theodore C Iancu. (2007) Ultrastructural features of lymphocyte suppression induced by anthrax lethal toxin and treated with chloroquine. Laboratory Investigation 87:2, 182-188
    CrossRef

96. 96

    Urszula Kosinska, Cecilia Carnrot, Michael P. B. Sandrini, Anders R. Clausen, Liya Wang, Jure Piskur, Staffan Eriksson, Hans Eklund. (2007) Structural studies of thymidine kinases from Bacillusanthracis and Bacilluscereus provide insights into quaternary structure and conformational changes upon substrate binding. FEBS Journal 274:3, 727-737
    CrossRef

97. 97

    Marcus Panning, Stefanie Kramme, Nadine Petersen, Christian Drosten. (2007) High throughput screening for spores and vegetative forms of pathogenic B. anthracis by an internally controlled real-time PCR assay with automated DNA preparation. Medical Microbiology and Immunology 196:1, 41-50
    CrossRef

98. 98

    Sarah Donegan, Richard Bellamy, Carrol L Gamble, Sarah Donegan. 2007. Vaccines for preventing anthrax. .
    CrossRef

99. 99

    G. R. Hemalatha, D. Satyanarayana Rao, L. Guruprasad. (2007) Identification and Analysis of Novel Amino-Acid Sequence Repeats in Bacillus anthracis str. Ames Proteome Using Computational Tools. Comparative and Functional Genomics 2007, 1-23
    CrossRef

100. 100

     Kadir Aslan, Yongxia Zhang, Stephen Hibbs, Les Baillie, Michael J. R. Previte, Chris D. Geddes. (2007) Microwave-accelerated metal-enhanced fluorescence: application to detection of genomic and exosporium anthrax DNA in <30 seconds. The Analyst 132:11, 1130
     CrossRef

101. 101

     Michael J McConnell, Philip C Hanna, Michael J Imperiale. (2007) Adenovirus-based Prime-boost Immunization for Rapid Vaccination Against Anthrax. Molecular Therapy 15:1, 203-210
     CrossRef

102. 102

     Federica Dal Molin, Fiorella Tonello, Daniel Ladant, Irene Zornetta, Ilaria Zamparo, Giulietta Di Benedetto, Manuela Zaccolo, Cesare Montecucco. (2006) Cell entry and cAMP imaging of anthrax edema toxin. The EMBO Journal 25:22, 5405-5413
     CrossRef

103. 103

     Aletta Ann Frazier, Teri J. Franks, Jeffrey R. Galvin. (2006) Inhalational Anthrax. Journal of Thoracic Imaging 21:4, 252-258
     CrossRef

104. 104

     Michael Donaghy. (2006) Neurologists and the threat of bioterrorism. Journal of the Neurological Sciences 249:1, 55-62
     CrossRef

105. 105

     Hanefi Yildirim, Nimet Kabakus, Mustafa Koc, Ayse Murat, Feyza İnceköy Girgin. (2006) Meningoencephalitis due to anthrax: CT and MR findings. Pediatric Radiology 36:11, 1190-1193
     CrossRef

106. 106

     Guan-Sheng Jiao, Ondrej Simo, Melissa Nagata, Sean O’Malley, Thomas Hemscheidt, Lynne Cregar, Sherri Z. Millis, Mark E. Goldman, Cho Tang. (2006) Selectively guanidinylated derivatives of neamine. Syntheses and inhibition of anthrax lethal factor protease. Bioorganic & Medicinal Chemistry Letters 16:19, 5183-5189
     CrossRef

107. 107

     Christopher Premanandan, Michael D. Lairmore, Soledad Fernandez, Andrew J. Phipps. (2006) Quantitative measurement of anthrax toxin receptor messenger RNA in primary mononuclear phagocytes. Microbial Pathogenesis 41:4-5, 193-198
     CrossRef

108. 108

     Haijing Hu, Qila Sa, Theresa M. Koehler, Arthur I. Aronson, Daoguo Zhou. (2006) Inactivation of Bacillus anthracis spores in murine primary macrophages. Cellular Microbiology 8:10, 1634-1642
     CrossRef

109. 109

     Farhang Babamahmoodi, Fereshteh Aghabarari, Abbas Arjmand, G. Hossein Ashrafi. (2006) Three rare cases of anthrax arising from the same source. Journal of Infection 53:4, e175-e179
     CrossRef

110. 110

     L.W.J. Baillie. (2006) Past, imminent and future human medical countermeasures for anthrax. Journal of Applied Microbiology 101:3, 594-606
     CrossRef

111. 111

     Brian R. Sloat, Zhengrong Cui. (2006) Nasal immunization with a dual antigen anthrax vaccine induced strong mucosal and systemic immune responses against toxins and bacilli. Vaccine 24:40-41, 6405-6413
     CrossRef

112. 112

     Wendy A Keitel. (2006) Recombinant protective antigen 102 (rPA102): profile of a second-generation anthrax vaccine. Expert Review of Vaccines 5:4, 417-430
     CrossRef

113. 113

     Demetrios N. Kyriacou, Alys Adamski, Nancy Khardori. (2006) Anthrax: From Antiquity and Obscurity to a Front-Runner in Bioterrorism. Infectious Disease Clinics of North America 20:2, 227-251
     CrossRef

114. 114

     Denise J. Jamieson, Jane E. Ellis, Daniel B. Jernigan, Tracee A. Treadwell. (2006) Emerging infectious disease outbreaks: Old lessons and new challenges for obstetrician-gynecologists. American Journal of Obstetrics and Gynecology 194:6, 1546-1555
     CrossRef

115. 115

     Yusuf Yakupogullari, Nimet Kabakus, Mehtap Durukan, Ahmet Kizirgil, Yasemin Bulut, Mustafa Yilmaz. (2006) Anthrax Meningoencephalitis Secondary to Oral Infection. The Pediatric Infectious Disease Journal 25:6, 572-573
     CrossRef

116. 116

     Thomas R. Howdieshell, Daithi Heffernan, Joseph T. Dipiro. (2006) Surgical Infection Society Guidelines for Vaccination after Traumatic Injury. Surgical Infections 7:3, 275-303
     CrossRef

117. 117

     Brian R. Sloat, Zhengrong Cui. (2006) Nasal Immunization with Anthrax Protective Antigen Protein Adjuvanted with Polyriboinosinic–Polyribocytidylic Acid Induced Strong Mucosal and Systemic Immunities. Pharmaceutical Research 23:6, 1217-1226
     CrossRef

118. 118

     Gerard G. Nahum, Kathleen Uhl, Dianne L. Kennedy. (2006) Antibiotic Use in Pregnancy and Lactation. Obstetrics & Gynecology 107:5, 1120-1138
     CrossRef

119. 119

     Ren Zhang, Chun-Ting Zhang. (2006) The impact of comparative genomics on infectious disease research. Microbes and Infection 8:6, 1613-1622
     CrossRef

120. 120

     Jeffrey F. Kuhn, Patric Hoerth, Silvia T. Hoehn, Tobias Preckel, Kenneth B. Tomer. (2006) Proteomics study of anthrax lethal toxin-treated murine macrophages. ELECTROPHORESIS 27:8, 1584-1597
     CrossRef

121. 121

     Scott Duong, Lucius Chiaraviglio, James E. Kirby. (2006) Histopathology in a murine model of anthrax. International Journal of Experimental Pathology 87:2, 131-137
     CrossRef

122. 122

     Brian R. Sloat, Zhengrong Cui. (2006) Evaluation of the immune response induced by a nasal anthrax vaccine based on the protective antigen protein in anaesthetized and non-anaesthetized mice. Journal of Pharmacy and Pharmacology 58:4, 439-447
     CrossRef

123. 123

     Guan-Sheng Jiao, Lynne Cregar, Mark E. Goldman, Sherri Z. Millis, Cho Tang. (2006) Guanidinylated 2,5-dideoxystreptamine derivatives as anthrax lethal factor inhibitors. Bioorganic & Medicinal Chemistry Letters 16:6, 1527-1531
     CrossRef

124. 124

     Yusheng Xiong, Judyann Wiltsie, Andrea Woods, Jian Guo, James V. Pivnichny, Wei Tang, Alka Bansal, Richard T. Cummings, Barry R. Cunningham, Arthur M. Friedlander, Cameron M. Douglas, Scott P. Salowe, Dennis M. Zaller, Edward M. Scolnick, Dennis M. Schmatz, Kenneth Bartizal, Jeffrey D. Hermes, Malcolm MacCoss, Kevin T. Chapman. (2006) The discovery of a potent and selective lethal factor inhibitor for adjunct therapy of anthrax infection. Bioorganic & Medicinal Chemistry Letters 16:4, 964-968
     CrossRef

125. 125

     Brian R. Sloat, Zhengrong Cui. (2006) Strong Mucosal and Systemic Immunities Induced by Nasal Immunization with Anthrax Protective Antigen Protein Incorporated in Liposome–Protamine–DNA Particles. Pharmaceutical Research 23:2, 262-269
     CrossRef

126. 126

     Gary S. Settles. (2006) FLUID MECHANICS AND HOMELAND SECURITY. Annual Review of Fluid Mechanics 38:1, 87-110
     CrossRef

127. 127

     Vladimir A. Karginov, Adiamseged Yohannes, Tanisha M. Robinson, Nour Eddine Fahmi, Kenneth Alibek, Sidney M. Hecht. (2006) β-Cyclodextrin derivatives that inhibit anthrax lethal toxin. Bioorganic & Medicinal Chemistry 14:1, 33-40
     CrossRef

128. 128

     Kazushige IJUIN, Fumiyo KUSU, Rieko MATSUDA, Yuzuru HAYASHI. (2006) A Method for Detecting Injury of People's Health from Prescriptions at a Pharmacy. YAKUGAKU ZASSHI 126:4, 283-287
     CrossRef

129. 129

     Patrick J. Neligan. 2006. Infectious Diseases and Bioterrorism. , 377-411.
     CrossRef

130. 130

     Mingtao Zeng, Qingfu Xu, Eric D. Hesek, Michael E. Pichichero. (2006) N-fragment of edema factor as a candidate antigen for immunization against anthrax. Vaccine 24:5, 662-670
     CrossRef

131. 131

     Katie A. Edwards, Harriet A. Clancy, Antje J. Baeumner. (2006) Bacillus anthracis: toxicology, epidemiology and current rapid-detection methods. Analytical and Bioanalytical Chemistry 384:1, 73-84
     CrossRef

132. 132

     Sheeba Alam, Megha Gupta, Rakesh Bhatnagar. (2006) Inhibition of platelet aggregation by anthrax edema toxin. Biochemical and Biophysical Research Communications 339:1, 107-114
     CrossRef

133. 133

     D. L. Stevens, A. L. Bisno, H. F. Chambers, E. D. Everett, P. Dellinger, E. J. C. Goldstein, S. L. Gorbach, J. V. Hirschmann, E. L. Kaplan, J. G. Montoya, J. C. Wade. (2005) Practice Guidelines for the Diagnosis and Management of Skin and Soft-Tissue Infections. Clinical Infectious Diseases 41:10, 1373-1406
     CrossRef

134. 134

     E. Erkek, E. Ayaslioglu, B. Beygo, U. Ozluk. (2005) An unusually extensive case of cutaneous anthrax in a patient with type II diabetes mellitus. Clinical and Experimental Dermatology 30:6, 652-654
     CrossRef

135. 135

     Jin Ho Moon, Joon Kyu Park, Eunice EunKyeong Kim. (2005) Structure analysis of peptide deformylase from Bacillus cereus. Proteins: Structure, Function, and Bioinformatics 61:1, 217-220
     CrossRef

136. 136

     Keiko Tomioka, Michael Peredelchuk, Xiangyang Zhu, Roberto Arena, Dmitri Volokhov, Angamuthu Selvapandiyan, Katie Stabler, Jenny Mellquist-Riemenschneider, Vladimir Chizhikov, Gerardo Kaplan, Hira Nakhasi, Robert Duncan. (2005) A Multiplex Polymerase Chain Reaction Microarray Assay to Detect Bioterror Pathogens in Blood. The Journal of Molecular Diagnostics 7:4, 486-494
     CrossRef

137. 137

     H. C. Baggett, J. C. Rhodes, S. K. Fridkin, C. P. Quinn, J. C. Hageman, C. R. Friedman, C. A. Dykewicz, V. A. Semenova, S. Romero-Steiner, C. M. Elie, J. A. Jernigan. (2005) No Evidence of a Mild Form of Inhalational Bacillus anthracis Infection During a Bioterrorism-Related Inhalational Anthrax Outbreak in Washington, D.C., in 2001. Clinical Infectious Diseases 41:7, 991-997
     CrossRef

138. 138

     Tara Wahab, Sandra Hjalmarsson, Ralfh Wollin, Lars Engstrand. (2005) Pyrosequencing Bacillus anthracis. Emerging Infectious Diseases 11:10, 1527-1531
     CrossRef

139. 139

     Trudy Adams, Sancha Osborn, Sjoerd Rijpkema. (2005) An immuno-diffusion assay to assess the protective antigen content of anthrax vaccine. Vaccine 23:36, 4517-4520
     CrossRef

140. 140

     Mehdi M. D. Numa, Lac V. Lee, Che-Chang Hsu, Kristen E. Bower, Chi-Huey Wong. (2005) Identification of Novel Anthrax Lethal Factor Inhibitors Generated by Combinatorial Pictet-Spengler Reaction Followed by Screening in situ. ChemBioChem 6:6, 1002-1006
     CrossRef

141. 141

     Robert N. Brey. (2005) Molecular basis for improved anthrax vaccines. Advanced Drug Delivery Reviews 57:9, 1266-1292
     CrossRef

142. 142

     James J Sejvar, Fred C Tenover, David S Stephens. (2005) Management of anthrax meningitis. The Lancet Infectious Diseases 5:5, 287-295
     CrossRef

143. 143

     Anthony W. Francis, Christy E. Ruggiero, Andrew T. Koppisch, Jingao Dong, Jian Song, Thomas Brettin, Srinivas Iyer. (2005) Proteomic analysis of Bacillus anthracis Sterne vegetative cells. Biochimica et Biophysica Acta (BBA) - Proteins & Proteomics 1748:2, 191-200
     CrossRef

144. 144

     Gene Godbold. 2005. Anthrax ( Bacillus Anthracis ). .
     CrossRef

145. 145

     Janusz J. Godyn, Luis Reyes, Richard Siderits, Anup Hazra. (2005) Cutaneous Anthrax. Advances in Skin & Wound Care 18:3, 146-150
     CrossRef

146. 146

     B.W. Gutting, K.S. Gaske, A.S. Schilling, A.F. Slaterbeck, L. Sobota, R.S. Mackie, T.L. Buhr. (2005) Differential susceptibility of macrophage cell lines to Bacillus anthracis–Vollum 1B. Toxicology in Vitro 19:2, 221-229
     CrossRef

147. 147

     Julie L. Boyer, Gary Kobinger, James M. Wilson, Ronald G. Crystal. (2005) Adenovirus-Based Genetic Vaccines for Biodefense. Human Gene Therapy 16:2, 157-168
     CrossRef

148. 148

     Micha Fridman, Valery Belakhov, Lac V. Lee, Fu-Sen Liang, Chi-Huey Wong, Timor Baasov. (2005) Dual Effect of Synthetic Aminoglycosides: Antibacterial Activity againstBacillus anthracis and Inhibition of Anthrax Lethal Factor. Angewandte Chemie 117:3, 451-456
     CrossRef

149. 149

     Micha Fridman, Valery Belakhov, Lac V. Lee, Fu-Sen Liang, Chi-Huey Wong, Timor Baasov. (2005) Dual Effect of Synthetic Aminoglycosides: Antibacterial Activity againstBacillus anthracis and Inhibition of Anthrax Lethal Factor. Angewandte Chemie International Edition 44:3, 447-452
     CrossRef

150. 150

     Ernest R. Blatchley, Anne Meeusen, Arthur I. Aronson, Lindsay Brewster. (2005) Inactivation of Bacillus Spores by Ultraviolet or Gamma Radiation. Journal of Environmental Engineering 131:9, 1245
     CrossRef

151. 151

     Manoj Karwa, Brian Currie, Vladmir Kvetan. (2005) Bioterrorism: Preparing for the impossible or the improbable. Critical Care Medicine 33:Supplement, S75-S95
     CrossRef

152. 152

     Şaban Gürcan, Filiz Akata, Figen Kuloğlu, Sevinç Erdoğan, Murat Tuğrul. (2005) Meningitis Due to Bacillus Anthracis. Yonsei Medical Journal 46:1, 159
     CrossRef

153. 153

     2004. Meeting the Needs of Children. .
     CrossRef

154. 154

     2004. Psychological Factors in Patients and the Public. .
     CrossRef

155. 155

     Darrell R Galloway, Les Baillie. (2004) DNA vaccines against anthrax. Expert Opinion on Biological Therapy 4:10, 1661-1667
     CrossRef

156. 156

     Janusz J. Godyn, Barbara Dotsey. (2004) Prevalence of presumptive Bacillus anthracis in the human population examined by nasal swabs. American Journal of Infection Control 32:6, 355-357
     CrossRef

157. 157

     Jeff Whiteaker, Jeffrey Karns, Catherine Fenselau, Michael L. Perdue. (2004) Analysis of Bacillus anthracis Spores in Milk Using Mass Spectrometry. Foodborne Pathogens and Disease 1:3, 185-194
     CrossRef

158. 158

     Dmitriy Volokhov, Andrei Pomerantsev, Violetta Kivovich, Avraham Rasooly, Vladimir Chizhikov. (2004) Identification of Bacillus anthracis by multiprobe microarray hybridization. Diagnostic Microbiology and Infectious Disease 49:3, 163-171
     CrossRef

159. 159

     Daniel De Palmenaer, Céline Vermeiren, Jacques Mahillon. (2004) IS231-MIC231 elements from Bacillus cereus sensu lato are modular. Molecular Microbiology 53:2, 457-467
     CrossRef

160. 160

     Rongguang Zhang, Ruiying Wu, Grazyna Joachimiak, Sarkis K Mazmanian, Dominique M Missiakas, Piotr Gornicki, Olaf Schneewind, Andrzej Joachimiak. (2004) Structures of Sortase B from Staphylococcus aureus and Bacillus anthracis Reveal Catalytic Amino Acid Triad in the Active Site. Structure 12:7, 1147-1156
     CrossRef

161. 161

     Dal-Hee Min, Wei-Jen Tang, Milan Mrksich. (2004) Chemical screening by mass spectrometry to identify inhibitors of anthrax lethal factor. Nature Biotechnology 22:6, 717-723
     CrossRef

162. 162

     Elizabeth A. Casman. (2004) The Potential of Next-Generation Microbiological Diagnostics to Improve Bioterrorism Detection Speed. Risk Analysis 24:3, 521-536
     CrossRef

163. 163

     Allison J. Beitel, Karen L. Olson, Ben Y. Reis, Kenneth D. Mandl. (2004) Use of Emergency Department Chief Complaint and Diagnostic Codes for Identifying Respiratory Illness in a Pediatric Population. Pediatric Emergency Care 20:6, 355-360
     CrossRef

164. 164

     B. Spellberg, J. H. Powers, E. P. Brass, L. G. Miller, J. E. Edwards. (2004) Trends in Antimicrobial Drug Development: Implications for the Future. Clinical Infectious Diseases 38:9, 1279-1286
     CrossRef

165. 165

     Taia T Wang, Patricia F Fellows, Terrance J Leighton, Alexander H Lucas. (2004) Induction of opsonic antibodies to the γ-d-glutamic acid capsule of Bacillus anthracis by immunization with a synthetic peptide-carrier protein conjugate. FEMS Immunology & Medical Microbiology 40:3, 231-237
     CrossRef

166. 166

     Yuequan Shen, Qing Guo, Natalia L. Zhukovskaya, Chester L. Drum, Andrew Bohm, Wei-Jen Tang. (2004) Structure of anthrax edema factor–calmodulin–adenosine 5′-(α,β-methylene)-triphosphate complex reveals an alternative mode of ATP binding to the catalytic site. Biochemical and Biophysical Research Communications 317:2, 309-314
     CrossRef

167. 167

     Morad Hassani, Mahesh C Patel, Liise-anne Pirofski. (2004) Vaccines for the prevention of diseases caused by potential bioweapons. Clinical Immunology 111:1, 1-15
     CrossRef

168. 168

     Bruce K. Hope. (2004) Using Fault Tree Analysis to Assess Bioterrorist Risks to the U.S. Food Supply. Human and Ecological Risk Assessment: An International Journal 10:2, 327-347
     CrossRef

169. 169

     L. V. M. Rao, M. Ngyuen, U. R. Pendurthi. (2004) Lethal toxin of Bacillus anthracis inhibits tissue factor expression in vascular cells. Journal of Thrombosis and Haemostasis 2:3, 530-532
     CrossRef

170. 170

     Taro Fukao. (2004) Immune system paralysis by anthrax lethal toxin: the roles of innate and adaptive immunity. The Lancet Infectious Diseases 4:3, 166-170
     CrossRef

171. 171

     Fiorella Tonello, Laura Naletto, Vanina Romanello, Federica Dal Molin, Cesare Montecucco. (2004) Tyrosine-728 and glutamic acid-735 are essential for the metalloproteolytic activity of the lethal factor of Bacillus anthracis. Biochemical and Biophysical Research Communications 313:3, 496-502
     CrossRef

172. 172

     Stephen Cendrowski, William MacArthur, Philip Hanna. (2004) Bacillus anthracis requires siderophore biosynthesis for growth in macrophages and mouse virulence. Molecular Microbiology 51:2, 407-417
     CrossRef

173. 173

     Vladimir P. Reshetin, James L. Regens. (2003) Simulation Modeling of Anthrax Spore Dispersion in a Bioterrorism Incident. Risk Analysis 23:6, 1135-1145
     CrossRef

174. 174

     Babak Mokhlesi, Thomas Corbridge. (2003) Toxicology in the critically ill patient. Clinics in Chest Medicine 24:4, 689-711
     CrossRef

175. 175

     Yadi Tan, Neil R. Hackett, Julie L. Boyer, Ronald G. Crystal. (2003) Protective Immunity Evoked Against Anthrax Lethal Toxin After a Single Intramuscular Administration of an Adenovirus-Based Vaccine Encoding Humanized Protective Antigen. Human Gene Therapy 14:17, 1673-1682
     CrossRef

176. 176

     Stephen W. Chensue. (2003) Exposing a Killer. The American Journal of Pathology 163:5, 1699-1702
     CrossRef

177. 177

     Annie H. Shinn, Normita C. Bravo, Holden T. Maecker, James W. Smith. (2003) TNF-α detection using a flow cytometric assay to determine cellular responses to anthrax vaccine. Journal of Immunological Methods 282:1-2, 169-174
     CrossRef

178. 178

     M. E. Jones, J. Goguen, I. A. Critchley, D. C. Draghi, J. A. Karlowsky, D. F. Sahm, R. Porschen, G. Patra, V. G. DelVecchio. (2003) Antibiotic susceptibility of isolates of Bacillus anthracis, a bacterial pathogen with the potential to be used in biowarfare. Clinical Microbiology and Infection 9:9, 984-986
     CrossRef

179. 179

     Alice S. Prince. (2003) The host response to anthrax lethal toxin: unexpected observations. Journal of Clinical Investigation 112:5, 656-658
     CrossRef

180. 180

     Jan K. Horn. (2003) Bacterial Agents Used for Bioterrorism. Surgical Infections 4:3, 281-287
     CrossRef

181. 181

     Marcia A Firmani, Larry A Broussard. (2003) Molecular diagnostic techniques for use in response to bioterrorism. Expert Review of Molecular Diagnostics 3:5, 605-616
     CrossRef

182. 182

     Amy E. Tucker, Isabelle I. Salles, Daniel E. Voth, William Ortiz-Leduc, Han Wang, Igor Dozmorov, Michael Centola, Jimmy D. Ballard. (2003) Decreased glycogen synthase kinase 3-beta levels and related physiological changes in Bacillus anthracis lethal toxin-treated macrophages. Cellular Microbiology 5:8, 523-532
     CrossRef

183. 183

     Jeannette Guarner, John A. Jernigan, Wun-Ju Shieh, Kathleen Tatti, Lisa M. Flannagan, David S. Stephens, Tanja Popovic, David A. Ashford, Bradley A. Perkins, Sherif R. Zaki. (2003) Pathology and Pathogenesis of Bioterrorism-Related Inhalational Anthrax. The American Journal of Pathology 163:2, 701-709
     CrossRef

184. 184

     Svetlana N. Radyuk, Patricia A. Mericko, Taissia G. Popova, Edith Grene, Ken Alibek. (2003) In vitro-generated respiratory mucosa: a new tool to study inhalational anthrax. Biochemical and Biophysical Research Communications 305:3, 624-632
     CrossRef

185. 185

     C. L. Cherry, M. A. Kainer, T. A. Ruff. (2003) Biological weapons preparedness: the role of physicians. Internal Medicine Journal 33:5-6, 242-253
     CrossRef

186. 186

     Hillary E Sussman. (2003) Spinach makes a safer anthrax vaccine. Drug Discovery Today 8:10, 428-430
     CrossRef

187. 187

     Timothy D. Read, Scott N. Peterson, Nicolas Tourasse, Les W. Baillie, Ian T. Paulsen, Karen E. Nelson, Hervé Tettelin, Derrick E. Fouts, Jonathan A. Eisen, Steven R. Gill, Erik K. Holtzapple, Ole Andreas Økstad, Erlendur Helgason, Jennifer Rilstone, Martin Wu, James F. Kolonay, Maureen J. Beanan, Robert J. Dodson, Lauren M. Brinkac, Michelle Gwinn, Robert T. DeBoy, Ramana Madpu, Sean C. Daugherty, A. Scott Durkin, Daniel H. Haft, William C. Nelson, Jeremy D. Peterson, Mihai Pop, Hoda M. Khouri, Diana Radune, Jonathan L. Benton, Yasmin Mahamoud, Lingxia Jiang, Ioana R. Hance, Janice F. Weidman, Kristi J. Berry, Roger D. Plaut, Alex M. Wolf, Kisha L. Watkins, William C. Nierman, Alyson Hazen, Robin Cline, Caroline Redmond, Joanne E. Thwaite, Owen White, Steven L. Salzberg, Brendan Thomason, Arthur M. Friedlander, Theresa M. Koehler, Philip C. Hanna, Anne-Brit Kolstø, Claire M. Fraser. (2003) The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria. Nature 423:6935, 81-86
     CrossRef

188. 188

     Jeffrey L Lange, Sandra E Lesikar, Mark V Rubertone, John F Brundage. (2003) Comprehensive systematic surveillance for adverse effects of Anthrax Vaccine Adsorbed, US Armed Forces, 1998–2000. Vaccine 21:15, 1620-1628
     CrossRef

189. 189

     Colleen M. Terriff, Mike D. Schwartz, Ben M. Lomaestro. (2003) Bioterrorism: Pivotal Clinical Issues. Pharmacotherapy 23:3, 274-290
     CrossRef

190. 190

     Matthew J. Kuehnert, Timothy J. Doyle, Holly A. Hill, Carolyn B. Bridges, John A. Jernigan, Peter M. Dull, Dori B. Reissman, David A. Ashford, Daniel B. Jernigan. (2003) Clinical Features that Discriminate Inhalational Anthrax from Other Acute Respiratory Illnesses. Clinical Infectious Diseases 36:3, 328-336
     CrossRef

191. 191

     Jessica Stern. (2003) Dreaded Risks and the Control of Biological Weapons. International Security 27:3, 89-123
     CrossRef

192. 192

     Sandy Bogucki, Scott Weir. (2002) Pulmonary manifestations of intentionally released chemical and biological agents. Clinics in Chest Medicine 23:4, 777-794
     CrossRef

193. 193

     J. David Roccaforte, James G. Cushman. (2002) Disaster preparation and management for the intensive care unit. Current Opinion in Critical Care 8:6, 607-615
     CrossRef

194. 194

     Itzhak Brook. (2002) The prophylaxis and treatment of anthrax. International Journal of Antimicrobial Agents 20:5, 320-325
     CrossRef

195. 195

     John H. Rex, Michael A. Pfaller. (2002) Has Antifungal Susceptibility Testing Come of Age?. Clinical Infectious Diseases 35:8, 982-989
     CrossRef

196. 196

     Pradeep K. Dhal, S. Randall Holmes-Farley, W. Harry Mandeville, Thomas X. Neenan. 2002. Polymeric Drugs. .
     CrossRef

197. 197

     GUY PATRA, LEANNE E. WILLIAMS, YUAN QI, SHARON ROSE, RAJENDRA REDKAR, VITO G. DELVECCHIO. (2002) Rapid Genotyping of Bacillus anthracis Strains by Real-Time Polymerase Chain Reaction. Annals of the New York Academy of Sciences 969:1, 106-111
     CrossRef

198. 198

     E. Nulens, A. Voss. (2002) Laboratory diagnosis and biosafety issues of biological warfare agents. Clinical Microbiology and Infection 8:8, 455-466
     CrossRef

199. 199

     A. Bryskier. (2002) Bacillus anthracis and antibacterial agents. Clinical Microbiology and Infection 8:8, 467-478
     CrossRef

200. 200

     Heinz Ellerbrok, Herbert Nattermann, Muhsin Ãzel, Lothar Beutin, Bernd Appel, Georg Pauli. (2002) Rapid and sensitive identification of pathogenic and apathogenic Bacillus anthracis by real-time PCR. FEMS Microbiology Letters 214:1, 51-59
     CrossRef

201. 201

     Theodore J Cieslak, Thomas B Talbot, Bonnie H Hartstein. (2002) Biological warfare and the skin I: bacteria and toxins1 1The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as necessarily reflecting the views of the United States Army or the Brooke Army Medical Center.. Clinics in Dermatology 20:4, 346-354
     CrossRef

202. 202

     Charles E. Binkley, Sandro Cinti, Diane M. Simeone, Lisa M. Colletti. (2002) Bacillus Anthracis as an Agent of Bioterrorism. Annals of Surgery 236:1, 9-16
     CrossRef

203. 203

     C.Anthony Hart, Nicholas J Beeching. (2002) A spotlight on anthrax. Clinics in Dermatology 20:4, 365-375
     CrossRef

204. 204

     Mark R. Wallace, Braden R. Hale, Gregory C. Utz, Patrick E. Olson, Kenneth C. Earhart, Scott A. Thornton, Kenneth C. Hyams. (2002) Endemic Infectious Diseases of Afghanistan. Clinical Infectious Diseases 34:S5, S171-S207
     CrossRef

205. 205

     Michael Mourez, D.Borden Lacy, Kristina Cunningham, Rachel Legmann, Bret R Sellman, Jeremy Mogridge, R.John Collier. (2002) 2001: a year of major advances in anthrax toxin research. Trends in Microbiology 10:6, 287-293
     CrossRef

206. 206

     Ronald A. Greenfield, Douglas A. Drevets, Linda J. Machado, Gene W. Voskuhl, Paul Cornea, Michael S. Bronze. (2002) Bacterial Pathogens as Biological Weapons and Agents of Bioterrorism. The American Journal of the Medical Sciences 323:6, 299-315
     CrossRef

207. 207

     Erwin Kurt Cullamar, Larry I. Lutwick. (2002) Inhalational anthrax. Current Infectious Disease Reports 4:3, 238-243
     CrossRef

208. 208

     Guy Patra, Agnès Fouet, Josée Vaissaire, Jean-Luc Guesdon, Michèle Mock. (2002) Variation in rRNA operon number as revealed by ribotyping of Bacillus anthracis strains. Research in Microbiology 153:3, 139-148
     CrossRef

209. 209

     John L. Sever, Alan I. Brenner, Arnold D. Gale, Jerry M. Lyle, Lawrence H. Moulton, David J. West. (2002) Safety of anthrax vaccine: a review by the Anthrax Vaccine Expert Committee (AVEC) of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS). Pharmacoepidemiology and Drug Safety 11:3, 189-202
     CrossRef

210. 210

     (2002) Cutaneous Anthrax Infection. New England Journal of Medicine 346:12, 945-946
     Full Text

211. 211

     Jeremy Sobel, Ali S Khan, David L Swerdlow. (2002) Threat of a biological terrorist attack on the US food supply: the CDC perspective. The Lancet 359:9309, 874-880
     CrossRef

212. 212

     Robert Kreitman. 2002. Exotoxins. .
     CrossRef

213. 213

     Ergin Ciftci, Erdal Ince, Ulker Dogru. (2002) Traditions, Anthrax, and Children. Pediatric Dermatology 19:1, 36-38
     CrossRef

214. 214

     Eric Lewin Altschuler. (2002) ACTH analogue in treatment of acute aortic dissection. The Lancet 359:9301, 168-169
     CrossRef

215. 215

     JOSEPH P. DUDLEY, MICHAEL H. WOODFORD. (2002) Bioweapons, Biodiversity, and Ecocide: Potential Effects of Biological Weapons on Biological Diversity. BioScience 52:7, 583
     CrossRef

216. 216

     Mark Rosenbloom, Jerrold B. Leikin, Stephen N. Vogel, Zafar A. Chaudry. (2002) Biological and Chemical Agents: A Brief Synopsis. American Journal of Therapeutics 9:1, 5-14
     CrossRef

217. 217

     Patrick J. Bradley, Alfio Ferlito, Margaret S. Brandwein, Michael S. Benninger, Alessandra Rinaldo. (2002) Anthrax: What Should the Otolaryngologist Know?. Acta Oto-laryngologica 122:6, 580-585
     CrossRef

218. 218

     Annette G. Beck-Sickinger. (2002) Anthrax: Terror im Immunsystem. Nachrichten aus der Chemie 50:1, 42-45
     CrossRef

219. 219

     Chien-An Chen, Scott McN Sieburth, Athanasios Glekas, Gregory W Hewitt, George L Trainor, Susan Erickson-Viitanen, Sena S Garber, Beverly Cordova, Susan Jeffry, Ronald M Klabe. (2001) Drug design with a new transition state analog of the hydrated carbonyl: silicon-based inhibitors of the HIV protease. Chemistry & Biology 8:12, 1161-1166
     CrossRef

220. 220

     Elizabeth Ann Coleman. (2001) Anthrax. American Journal of Nursing 101:12, 48-52
     CrossRef

221. 221

     Phillip R Pittman, Paul H Gibbs, Timothy L Cannon, Arthur M Friedlander. (2001) Anthrax vaccine: short-term safety experience in humans. Vaccine 20:5-6, 972-978
     CrossRef

222. 222

     &NA;. (2001) Immediate identification and management of anthrax essential for optimal outcome. Drugs & Therapy Perspectives 17:24, 6-11
     CrossRef

223. 223

     Katarina Chiller, Bryan A. Selkin, George J. Murakawa. (2001) Skin Microflora and Bacterial Infections of the Skin. Journal of Investigative Dermatology Symposium Proceedings 6:3, 170-174
     CrossRef

224. 224

     Bush, Larry M., Abrams, Barry H., Beall, Anne, Johnson, Caroline C., . (2001) Index Case of Fatal Inhalational Anthrax Due to Bioterrorism in the United States. New England Journal of Medicine 345:22, 1607-1610
     Full Text

225. 225

     Swartz, Morton N., . (2001) Recognition and Management of Anthrax — An Update. New England Journal of Medicine 345:22, 1621-1626
     Full Text

226. 226

     The Editors. (2001) After September 11. New England Journal of Medicine 345:20, 1490-1490
     Full Text

227. 227

     Andrew D. Pannifer, Thiang Yian Wong, Robert Schwarzenbacher, Martin Renatus, Carlo Petosa, Jadwiga Bienkowska, D. Borden Lacy, R. John Collier, Sukjoon Park, Stephen H. Leppla, Philip Hanna, Robert C. Liddington. (2001) Crystal structure of the anthrax lethal factor. Nature 414:6860, 229-233
     CrossRef

228. 228

     Philip C. Hanna. (2001) Anthrax: A motor protein determines anthrax susceptibility. Current Biology 11:22, R905-R906
     CrossRef

229. 229

     L. Baillie. (2001) The development of new vaccines against Bacillus anthracis. Journal of Applied Microbiology 91:4, 609-613
     CrossRef

230. 230

     R.C. Spencer, N.F. Lightfoot. (2001) Preparedness and Response to Bioterrorism. Journal of Infection 43:2, 104-110
     CrossRef

231. 231

     Khan, Ali S., Ashford, David A., . (2001) Ready or Not — Preparedness for Bioterrorism. New England Journal of Medicine 345:4, 287-289
     Full Text

232. 232

     Renuka Heddurshetti, Wadchara Pumpradit, Larry I. Lutwick. (2001) Pulmonary manifestations of bioterrorism. Current Infectious Disease Reports 3:3, 249-257
     CrossRef

233. 233

     Lorna Schumann, Leslie Henry. (2001) Inhalational Anthrax: Threat, Clinical Presentation, and Treatment. Journal of the American Academy of Nurse Practitioners 13:4, 164-168
     CrossRef

234. 234

     Robert T. Chen, Frank DeStefano, Robert Pless, Gina Mootrey, Piotr Kramarz, Beth Hibbs. (2001) Challenges and Controversies in Immunization Safety. Infectious Disease Clinics of North America 15:1, 21-39
     CrossRef

235. 235

     Devinder M. Thappa, , Kaliaperumal Karthikeyan. (2001) Anthrax: an overview within the Indian subcontinent. International Journal of Dermatology 40:3, 216-222
     CrossRef

236. 236

     Les Baillie, Timothy D Read. (2001) Bacillus anthracis, a bug with attitude!. Current Opinion in Microbiology 4:1, 78-81
     CrossRef

237. 237

     David J. Weber, William A. Rutala. (2001) Risks and Prevention of Nosocomial Transmission of Rare Zoonotic Diseases. Clinical Infectious Diseases 32:3, 446
     CrossRef

238. 238

     Birdal Yorgancigil, Mustafa Demirci, Mehmet Unlu, Erdogan Sevük, Mehmet Doganay. (2001) Anthrax meningitis: Case report. International Journal of Infectious Diseases 5:4, 220-221
     CrossRef

239. 239

     Terry C. Dixon, Amin A. Fadl, Theresa M. Koehler, Joel A. Swanson, Philip C. Hanna. (2000) Early Bacillus anthracis-macrophage interactions: intracellular survival and escape. Cellular Microbiology 2:6, 453-463
     CrossRef

240. 240

     (2000) Anthrax. New England Journal of Medicine 342:1, 61-62
     Full Text

241. 241

     T Jefferson, V Demicheli, J Deeks, P Graves, M Pratt, D Rivetti, Tom Jefferson. 1998. Vaccines for preventing anthrax. .
     CrossRef

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